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Abstract Background The cycle threshold (Ct) value is inversely proportional to the number of copies of the target region in a sample, suggesting that a low Ct value indicates a high pathogen load. The relationship between Ct value and clinical presentation in children with pertussis is not well-defined. Methods We investigated the relationships between the Ct value of nasopharyngeal samples positive for Bordetella pertussis deoxyribonucleic acid via real-time polymerase chain reaction (PCR), collected from children on admission and their adult family members between May 2022 and March 2024 at Hangzhou Children’s Hospital, China. The study focused on the correlation between Ct value and clinical presentation in children with pertussis. Results The Ct value was positively correlated with age (r = 0.362, P = 0.001). The mean Ct value for children with pertussis was 28.0 (range: 22.0–32.0), which was lower than the 32.0 (range: 30.0–34.0) observed in adults. Ct value was inversely correlated with length of stay, an indicator of disease severity (r = -0.356, P = 0.001). Logistic regression analyses revealed that both Ct value (OR: 0.891, 95% CI: 0.799–0.993, P = 0.036) and white blood cell count (OR: 1.127, 95% CI: 1.005–1.263, P = 0.040) were independently associated with severity of pertussis. Conclusions Real-time PCR Ct values at initial diagnosis for pertussis may potentially predict severe disease outcomes in children.

Abstract Background Pediatric bacterial meningitis (PBM) remains a devastating disease that causes substantial neurological morbidity and mortality worldwide. However, there are few large-scale studies on the pathogens causing PBM and their antimicrobial resistance (AMR) patterns in China. The present multicenter survey summarized the features of the etiological agents of PBM and characterized their AMR patterns. Methods Patients diagnosed with PBM were enrolled retrospectively at 13 children’s hospitals in China from 2016 to 2018 and were screened based on a review of cerebrospinal fluid (CSF) microbiology results. Demographic characteristics, the causative organisms and their AMR patterns were systematically analyzed. Results Overall, 1193 CSF bacterial isolates from 1142 patients with PBM were obtained. The three leading pathogens causing PBM were Staphylococcus epidermidis (16.5%), Escherichia coli (12.4%) and Streptococcus pneumoniae (10.6%). In infants under 3 months of age, the top 3 pathogens were E. coli (116/523; 22.2%), Enterococcus faecium (75/523; 14.3%), and S. epidermidis (57/523; 10.9%). However, in children more than 3 months of age, the top 3 pathogens were S. epidermidis (140/670; 20.9%), S. pneumoniae (117/670; 17.5%), and Staphylococcus hominis (57/670; 8.5%). More than 93.0% of E. coli isolates were sensitive to cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam, amikacin and carbapenems, and the resistance rates to ceftriaxone, cefotaxime and ceftazidime were 49.4%, 49.2% and 26.4%, respectively. From 2016 to 2018, the proportion of methicillin-resistant coagulase-negative Staphylococcus isolates (MRCoNS) declined from 80.5 to 72.3%, and the frequency of penicillin-resistant S. pneumoniae isolates increased from 75.0 to 87.5%. The proportion of extended-spectrum β-lactamase (ESBL)-producing E. coli fluctuated between 44.4 and 49.2%, and the detection rate of ESBL production in Klebsiella pneumoniae ranged from 55.6 to 88.9%. The resistance of E. coli strains to carbapenems was 5.0%, but the overall prevalence of carbapenem-resistant K. pneumoniae (CRKP) was high (54.5%). Conclusions S. epidermidis, E. coli and S. pneumoniae were the predominant pathogens causing PBM in Chinese patients. The distribution of PBM causative organisms varied by age. The resistance of CoNS to methicillin and the high incidence of ESBL production among E. coli and K. pneumoniae isolates were concerning. CRKP poses a critical challenge for the treatment of PBM.

Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions.Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children’s hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification.Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2% (n = 2,331) were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections (43.2%, n = 6,379). WHO Watch group antibiotics accounted for 70.4% of prescriptions (n = 12,915). The most prescribed antibiotic ATC classes were third-generation cephalosporins (41.9%, n = 7,679), followed by penicillins/β-lactamase inhibitors (16.1%, n = 2,962), macrolides (12.1%, n = 2,214) and carbapenems (7.7%, n = 1,331).Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented.

Abstract NRAS mutations are most frequently observed in hematological malignancies and are also common in some solid tumors such as melanoma and colon cancer. Despite its pivotal role in oncogenesis, no effective therapies targeting NRAS has been developed. Targeting NRAS localization to the plasma membrane (PM) is a promising strategy for cancer therapy, as its signaling requires PM localization. However, the process governing NRAS translocation from the Golgi apparatus to the PM after lipid modification remains elusive. This study identifies GOLGA7 as a crucial factor controlling NRAS’ PM translocation, demonstrating that its depletion blocks NRAS, but not HRAS, KRAS4A and KRAS4B, translocating to PM. GOLGA7 is known to stabilize the palmitoyltransferase ZDHHC9 for NRAS and HRAS palmitoylation, but we found that GOLGA7 depletion does not affect NRAS’ palmitoylation level. Further studies show that loss of GOLGA7 disrupts NRAS anterograde trafficking, leading to its cis-Golgi accumulation. Remarkably, depleting GOLGA7 effectively inhibits cell proliferation in multiple NRAS-mutant cancer cell lines and attenuates NRASG12D-induced oncogenic transformation in vivo. These findings elucidate a specific intracellular trafficking route for NRAS under GOLGA7 regulation, highlighting GOLGA7 as a promising therapeutic target for NRAS-driven cancers.

Abstract The two key problems of the in‐band ripples and out‐of‐band suppression are proposed in the design of the SAW yarn tension sensor and the methods of decreasing them are achieved. The unbalanced split‐electrode interdigital transducers (IDT) are designed so that the total phase of the regenerated reflection wave and mass load feedback is close to 180°, leading to an effective reduction of the in‐band ripples effect characterised by the sensor frequency response. The engraved bi‐directional slots on the back of the substrate can block the propagation path of the bulk acoustic wave (BAW) to a certain extent, reducing the influence of BAW propagation and suppressing the out‐of‐band suppression of the frequency response. The experimental results show that the SAW yarn tension sensor with the unbalanced split‐electrode IDT can reduce the in‐band ripples from 23.34 to 0.93 dB, and the engraved bi‐directional slots can suppress the out‐of‐band suppression from 28.03 to 7.71 dB.

Magnetic tunnel junction (MTJ) sensors have been one of the excellent candidates for magnetic field detection due to their high sensitivity and compact size. In this paper, we design a magnetometer with in situ magnetic feedback consisting of an MTJ sensor. To analyze and evaluate the detectivity of the MTJ magnetometer, a noise model of the MTJ sensor in the magnetometer without magnetic feedback is first developed. Then, the noise model of the MTJ magnetometer with in situ magnetic feedback is also established, including the noises of the MTJ sensor and the signal conditioning circuit, as well as the feedback circuit. The equivalent noise model of the MTJ magnetometer with in situ magnetic feedback is evaluated through nonlinear fitting for the noise voltage spectrum. Although the noise generated by the MTJ sensor is much greater than that of the signal conditioning circuit, the noise introduced by the feedback coils into the MTJ sensor is slightly more than twice that generated by the MTJ sensor itself. The measurement results show that the detectivity of the MTJ magnetometer with in situ magnetic feedback reaches 526 pT/Hz1/2 at 10 Hz. The equivalent noise analysis method presented in this paper is suitable for the detectivity analysis of magnetometers with magnetic feedback.

TP53-induced glycolysis and apoptosis regulator (TIGAR) alleviates oxidative stress and protects against ischemic neuronal injury by shifting glucose metabolism into the pentose phosphate pathway (PPP). However, the brain alters glucose metabolism from PPP to glycolysis during prolonged ischemia. It is still unknown whether and how TIGAR exerts the antioxidant activity and neuroprotection in prolonged ischemic brains. Here, we determined the significant upregulation of TIGAR that was proportional to the duration of ischemia. However, TIGAR failed to upregulate the NADPH level but still alleviated oxidative stress in neuronal cells with prolonged oxygen glucose-deprivation (OGD). Furthermore, inhibiting PPP activity, either by the expression of mutant TIGAR (which lacks enzymatic activity) or by silencing Glucose 6-phosphate dehydrogenase, still retained antioxidant effects and neuroprotection of TIGAR with prolonged OGD. Intriguingly, TIGAR-induced autophagy alleviated oxidative stress, contributing to neuron survival. Further experiments indicated that TIGAR-induced autophagy neutralized oxidative stress by activating Nrf2, which was cancelled by ML385 or Nrf2 knockdown. Remarkably, either Atg7 deletion or Nrf2 silencing abolished the neuroprotection of TIGAR in mice with prolonged ischemia. Taken together, we found a PPP-independent pathway in which TIGAR alleviates oxidative stress. TIGAR induces autophagy and, thus, activates Nrf2, offering sustainable antioxidant defense in brains with extended ischemia. This previously unexplored mechanism of TIGAR may serve as a critical compensation for antioxidant activity caused by the lack of glucose in ischemic stroke.

Neurotoxins generally inhibit or promote the release of neurotransmitters or bind to receptors that are located in the pre- or post-synaptic membranes, thereby affecting physiological functions of synapses and affecting biological processes. With more and more research on the toxins of various origins, many neurotoxins are now widely used in clinical treatment and have demonstrated good therapeutic outcomes. This review summarizes the structural properties and potential pharmacological effects of neurotoxins acting on different components of the synapse, as well as their important clinical applications, thus could be a useful reference for researchers and clinicians in the study of neurotoxins.

In this paper, we consider the control problem for multiplicative noise system with intermittent noise and input delay. For the finite-horizon case, in virtue of the dynamic programming approach, the optimal output feedback controller is proposed for the first time. For the infinite-horizon case, it is shown that the multiplicative noise system can be stabilized if and only if the given modified Riccati equation has the unique solution.

In this paper, the optimal continuous/impulsive linear quadratic (LQ) control problem with quadratic constraints is thoroughly solved for the first time. The main contributions of this paper can be stated as in the following. First, the maximum principle is developed by using the variational method. Then, by using the Lagrange duality principle, the optimal continuous/impulsive control can thus be obtained via decoupling the forward and backward differential/difference equation (FBSDE). Finally, the optimal parameter can be calculated by using the gradient-type optimization algorithm.

In an indoor environment, object identification and localization are paramount for human-object interaction. Visual or laser-based sensors can achieve the identification and localization of the object based on its appearance, but these approaches are computationally expensive and not robust against the environment with obstacles. Radio Frequency Identification (RFID) has a unique tag ID to identify the object, but it cannot accurately locate it. Therefore, in this paper, the data of RFID and laser range finder are fused for the better identification and localization of multiple dynamic objects in an indoor environment. The main method is to use the laser range finder to estimate the radial velocities of objects in a certain environment, and match them with the object’s radial velocities estimated by the RFID phase. The method also uses a fixed time series as “sliding time window” to find the cluster with the highest similarity of each RFID tag in each window. Moreover, the Pearson correlation coefficient (PCC) is used in the update stage of the particle filter (PF) to estimate the moving path of each cluster in order to improve the accuracy in a complex environment with obstacles. The experiments were verified by a SCITOS G5 robot. The results show that this method can achieve an matching rate of 90.18% and a localization accuracy of 0.33m in an environment with the presence of obstacles. This method effectively improves the matching rate and localization accuracy of multiple objects in indoor scenes when compared to the Bray-Curtis (BC) similarity matching-based approach as well as the particle filter-based approach.

MoS2 ultra-thin layers are synthesized using a chemical vapor deposition method based on the sulfurization of molybdenum trioxide (MoO3). The ultra-thin layers are characterized by X-ray diffraction (XRD), photoluminescence (PL) spectroscopy and atomic force microscope (AFM). Based on our experimental results, all the processing parameters, such as the tilt angle of substrate, applied voltage, heating time and the weight of source materials have effect on the microstructures of the layers. In this paper, the effects of such processing parameters on the crystal structures and morphologies of the as-grown layers are studied. It is found that the film obtained with the tilt angle of 0.06° is more uniform. A larger applied voltage is preferred to the growth of MoS2 thin films at a certain heating time. In order to obtain the ultra-thin layers of MoS2, the weight of 0.003 g of source materials is preferred. Under our optimal experimental conditions, the surface of the film is smooth and composed of many uniformly distributed and aggregated particles, and the ultra-thin MoS2 atomic layers (1∼10 layers) covers an area of more than 2 mm×2 mm.