Trans-spinal magnetic stimulation induces co-activation of the diaphragm and biceps in healthy subjects.

The present study was designed to examine the effect of trans-spinal magnetic stimulation on bilateral respiratory and forelimb muscles in healthy subjects. Two wings of a figure-of-eight magnetic coil were placed on the dorsal vertebrae, from the fifth cervical to the second thoracic dorsal vertebra with a center at the seventh cervical vertebra. The surface electromyograms of bilateral diaphragm and biceps were recorded in response to trans-spinal magnetic stimulation with 20%-100% maximum output of the stimulatory device in male (n = 12) and female participants (n = 8). Trans-spinal magnetic stimulation can induce a co-activation of bilateral diaphragm and biceps when the stimulation intensity is above 60%. The onset latency was comparable between the left and right sides of the muscles, suggesting bilateral muscles could be simultaneously activated by trans-spinal magnetic stimulation. In addition, the intensity-response curve of the biceps was shifted upward compared with that of the diaphragm in males, indicating that the responsiveness of the biceps was greater than that of the diaphragm. This study demonstrated the feasibility of utilizing trans-spinal magnetic stimulation to co-activate the bilateral diaphragm and biceps. We proposed that this stimulatory configuration can be an efficient approach to activate both respiratory and forelimb muscles.

An adaptive detection model for IPv6 extension header threats based on deterministic decision automaton.

The IPv6 extension header mechanism, a new feature of the IPv6 protocol, enhances flexibility and scalability but introduces numerous security threats like firewall evasion and covert channels. Existing threat detection methods face limitations in detection types, universality, and speed. Hence, an adaptive detection model for IPv6 extension header threats (ADM-DDA6) is proposed. Firstly, standard rule sets are designed for common IPv6 extension headers, successfully detecting 70 types of threats from THC-IPv6 and ExtHdr tools using only 20 rules. Secondly, by parsing IPv6 extension headers, matching rules, establishing transition relationships, and deciding packet threat status based on final states (Normal or Abnormal), complex threats like header disorder and header repetition can be detected. Finally, an adaptive rule matching method is introduced, which dynamically selects rule sets based on IPv6 extension header types, effectively reducing rule matching time. Experimental results show that under different threat magnitudes, ADM-DDA6 is 32% faster than Suricata v6.0.12 and 21.2% faster than Snort v3.1.61.0 in detection speed. Additionally, as the number of threats increases, on commodity hardware, ADM-DDA6 incurs only a 0.7% increase in CPU overhead with no significant memory consumption increase, maintains maximum throughput, and exhibits minor performance changes under low and moderate network load conditions.

Novel functions of o-cymen-5-ol nanoemulsion in reversing colistin resistance in multidrug-resistant Klebsiella pneumoniae infections.

Multidrug resistance (MDR) Klebsiella pneumoniae (K. pneumoniae) is a major emerging threat to human health, and leads to very high mortality rate. The effectiveness of colistin, the last resort against MDR Gram-negative bacteria, is significantly compromised due to the widespread presence of plasmid- or chromosome-mediated resistance genes. In this study, o-cymen-5-ol has been found to greatly restore colistin sensitivity in MDR K. pneumoniae. Importantly, this compound does not impact bacterial viability, induce resistance, or cause any noticeable cell toxicity. Various routes disclosed the potential mechanism of o-cymen-5-ol potentiating colistin activity against MDR K. pneumoniae. These include inhibiting the activity of plasmid-mediated mobile colistin resistance gene (mcr-1), accelerating lipopolysaccharide (LPS) - mediated membrane damage, and promoting the ATP-binding cassette (ABC) transporter pathway. To enhance the administration and bioavailability of o-cymen-5-ol, a nanoemulsion has been designed, which significantly improves the loading efficiency and solubility of o-cymen-5-ol, resulting in antimicrobial potentiation of colistin against K. pneumoniae infection. This study has revealed a new understanding of the o-cymen-5-ol nanoemulsion as a means to enhance the effectiveness of colistin against resistant factors. The finding also suggests that o-cymen-5-ol nanoemulsion could be a promising approach in the development of potential treatments for multidrug-resistant Gram-negative bacterial infections.

Expanding the genotypic and phenotypic spectrum associated with TBL1XR1 de novo variants.

BACKGROUND: The TBL1XR1 gene encodes the protein transducin-beta-like 1 receptor1, widely distributed in the pituitary, hypothalamus, white and brown adipose tissue, muscle, and liver. Current evidence suggests that heterozygous TBL1XR1 pathogenic variants can lead to a wide spectrum of phenotypes. This study aims to reveal the clinical phenotype and genetic profiles of de novo TBL1XR1 variations and summarize the relevant clinical and genetic features. METHODS: We analyzed four new cases harboring de novo TBL1XR1 variants and reviewed all reported cases. RESULTS: All probands suffered from global developmental delay. Moreover, patient 1 exhibited susceptibility to startle, patient 2 had hypovitaminosis D, short stature and hyponatremia, and patients 3 and 4 both presented with ASD (Autism spectrum disorder) and short stature. They all had a de novo TBL1XR1 variant (NM_024665.7), c.1184A > G (p.Tyr395Cys), c.1108G > A (p.Asp370Asn), c.1047 + 1G > C, and c.1097C > T (p.Ser366Phe) respectively. In addition, pooled analysis of 51 cases showed that they had speech impairment (38/39), intellectual developmental disorder (28/28), global developmental delay (42/42), and hypotonia (24/27), and some of them had epilepsy (10/22), ASD (13/25), and developmental regression (4/13). CONCLUSIONS: We report four new patients with de novo TBL1XR1 variants and provide a comprehensive overview of 47 previously reported individuals with TBL1XR1 variants, enriching the genotypic and phenotypic spectrum of TBL1XR1-related disease. This report further validates the pathogenicity de novo TBL1XR1 variants.

Position effect of trans-spinal magnetic stimulation on diaphragmatic motor evoked potential in healthy humans.

The present study was designed to evaluate the rostrocaudal and lateral-midline effects of trans-spinal magnetic stimulation on diaphragmatic motor evoked potential by utilizing a figure-of-eight coil. The bilateral diaphragm electromyograms were recorded during trans-spinal magnetic stimulation from 60% to 100% of maximum output in 21 healthy subjects. The rostrocaudal effect of trans-spinal magnetic stimulation was evaluated by comparing diaphragmatic motor evoked potential when the coil was placed at the midline of the fifth (C5) and seventh (C7) cervical vertebrae and the second thoracic vertebra (T2). The diaphragmatic motor evoked potential was also examined during midline and lateral (± 15 mm) trans-spinal magnetic stimulation to examine the lateral-midline effect. The results demonstrated that the amplitude of diaphragmatic motor evoked potential was not significantly different in response to C5, C7, or T2 trans-spinal magnetic stimulation. In addition, the sensitivity of the left and right diaphragms to trans-spinal magnetic stimulation was different, as reflected by a greater amplitude of the right diaphragmatic motor evoked potential during midline trans-spinal magnetic stimulation. Moreover, although midline trans-spinal magnetic stimulation could induce coactivation of the bilateral diaphragm, lateral trans-spinal magnetic stimulation can induce a greater motor evoked potential in the ipsilateral than the contralateral diaphragm. Finally, there was no significant sex effect on the diaphragmatic motor evoked potential induced by trans-spinal magnetic stimulation. These results suggest that trans-spinal magnetic stimulation using a figure-of-eight coil is feasible to induce diaphragmatic motor evoked potential, and there is a lateral-midline effect of trans-spinal magnetic stimulation on the bilateral diaphragm.NEW & NOTEWORTHY The present study investigated position effect of trans-spinal magnetic stimulation using figure-of-eight coil on diaphragm in healthy humans. The result demonstrated that midline trans-spinal magnetic stimulation induces coactivation of bilateral diaphragm, whereas lateral trans-spinal magnetic stimulation induces greater motor evoked potentials in the ipsilateral than the contralateral diaphragm. These results suggest that trans-spinal magnetic stimulation is feasible to induce diaphragmatic motor evoked potential, and there is a lateral-midline effect of trans-spinal magnetic stimulation on diaphragm.

Rostral-Caudal Effect of Cervical Magnetic Stimulation on the Diaphragm Motor Evoked Potential after Cervical Spinal Cord Contusion in the Rat.

The present study was designed to investigate the rostral-caudal effect of spinal magnetic stimulation on diaphragmatic motor-evoked potentials after cervical spinal cord injury. The diaphragm electromyogram was recorded in rats that received a laminectomy or a left midcervical contusion at the acute (1 day), subchronic (2 weeks), or chronic (8 weeks) injury stages. The center of a figure-eight coil was placed at 30 mm lateral to bregma on the left side, and the effect of magnetic stimulation was evaluated by stimulating the rostral, middle, and caudal cervical regions in spontaneously breathing rats. The results demonstrated that cervical magnetic stimulation induced intensity-dependent motor-evoked potentials in the bilateral diaphragm in both uninjured and contused rats; however, the left diaphragm exhibited a higher amplitude and earlier onset than the right diaphragm. Moreover, the intensity-response curve was shifted upward in the rostral-to-caudal direction of magnetic stimulation, suggesting that caudal cervical magnetic stimulation produced more robust diaphragmatic motor-evoked potentials compared with rostral cervical magnetic stimulation. Interestingly, the diaphragmatic motor-evoked potentials were similar between uninjured and contused rats during cervical magnetic stimulation despite weaker inspiratory diaphragmatic activity in contused rats. In addition, in contused animals but not uninjured animals, diaphragmatic motor-evoked potential amplitudes were greater at the chronic stage than during earlier injury stages. These results demonstrated that cervical magnetic stimulation can excite the residual phrenic motor circuit to activate the diaphragm in the presence of a significant lesion in the cervical spinal cord. These findings indicate that this non-invasive approach is effective for modulating diaphragmatic excitability after cervical spinal cord injury.

Microfluidic synthesis of Ag@Cu2O core-shell nanoparticles with enhanced photocatalytic activity.

A microfluidic-based method for the continuous synthesis of Ag@Cu2O core-shell nanoparticles (NPs) has been developed. It only took 32s to obtain Ag@Cu2O core-shell NPs, indicating a high efficiency of this microfluidic-based method. Triangular Ag nanoprisms were employed as the cores for the overgrowth of Cu2O through the reduction of Cu(OH)42- with ascorbic acid. The as-synthesized samples were characterized by XRD, TEM, SEM, HAADF-STEM, EDX, HRTEM, UV-vis spectra and N2 adsorption-desorption. The characterization results revealed that the as-synthesized Ag@Cu2O core-shell NPs exhibited a well-defined core-shell nanostructure with a polycrystalline shell, which was composed of numbers of Cu2O domains epitaxially growing on the triangular Ag nanoprism. It was concluded that the synthesis parameters such as the molar ratio of trisodium citrate to AgNO3, H2O2 to AgNO3, NaOH to CuSO4, ascorbic acid to CuSO4 and AgNO3 to CuSO4 had significant effect on the synthesis of Ag@Cu2O core-shell NPs. Moreover, Ag@Cu2O core-shell NPs exhibited superior catalytic activity in comparison with pristine Cu2O NPs towards the visible light-driven degradation of methyl orange. This enhanced photocatalytic activity of Ag@Cu2O core-shell NPs was attributed to the larger BET surface area and improved charge separation efficiency. The trapping experiment indicated that holes and superoxide anion radicals were the major reactive species in the photodegradation of methyl orange over Ag@Cu2O core-shell NPs. In addition, Ag@Cu2O core-shell NPs showed no obvious deactivation in the cyclic test.