Effectiveness of the enterovirus A71 vaccine on hand, foot and mouth disease: a real-world study in China.

OBJECTIVES: For the prevention of hand, foot and mouth disease (HFMD), enterovirus A71 (EV-A71) vaccines have been utilized in China since 2016. To better inform vaccination strategies, we assess the real-world effectiveness of EV-A71 vaccination in China. METHODS: The analysis was based on surveillance data of HFMD caused by EV-A71 in children under the age of five in China, along with meteorological and demographic data. The seasonal autoregressive integrated moving average model and the interrupted time-series analysis were used to estimate the effectiveness of the EV-A71 vaccination on the EV-A71 HFMD incidence and to predict the counterfactual cases with no EV-A71 vaccine. RESULTS: Between 2010 and 2018, 6,712,613 cases of HFMD caused by EV-A71 were reported in children under five years old in 260 Chinese cities. During 2017-2018, the EV-A71 vaccination was associated with a reduction in EV-A71 HFMD incidence, with a relative risk of 0.83 (95% confidence interval (CI): 0.81-0.86), and an estimated reduction of 297,946 (95% CI: 250,534-346,658) cases. However, this association varied across cities (I2=85.6%, P<0.001) and the effectiveness of EV-A71 vaccination decreased as population density increased. Higher vaccination coverage was associated with greater effectiveness of the EV-A71 vaccination and an earlier point in EV-A71 cases reduction. Specifically, when the vaccination coverage exceeded approximately 20%, the relative risk was rapidly reduced to below 0.71 (95% CI: 0.69-0.72). CONCLUSIONS: Our study demonstrated that the EV-A71 vaccination was associated with a reduction in the incidence of EV-A71 HFMD, but the association varied with regions and was influenced by vaccination coverage and population density. To optimize EV-A71 HFMD prevention, increasing vaccination coverage (over 20%) is recommended for children under five years old.

Dynamic modulation of nodulation factor receptor levels by phosphorylation-mediated functional switch of a RING-type E3 ligase during legume nodulation.

The precise control of receptor levels is crucial for initiating cellular signaling transduction in response to specific ligands; however, such mechanisms regulating nodulation factor (NF) receptor (NFR)-mediated perception of NFs to establish symbiosis remain unclear. In this study, we unveil the pivotal role of the NFR-interacting RING-type E3 ligase 1 (NIRE1) in regulating NFR1/NFR5 homeostasis to optimize rhizobial infection and nodule development in Lotus japonicus. We demonstrated that NIRE1 has a dual function in this regulatory process. It associates with both NFR1 and NFR5, facilitating their degradation through K48-linked polyubiquitination before rhizobial inoculation. However, following rhizobial inoculation, NFR1 phosphorylates NIRE1 at a conserved residue, Tyr-109, inducing a functional switch in NIRE1, which enables NIRE1 to mediate K63-linked polyubiquitination, thereby stabilizing NFR1/NFR5 in infected root cells. The introduction of phospho-dead NIRE1Y109F leads to delayed nodule development, underscoring the significance of phosphorylation at Tyr-109 in orchestrating symbiotic processes. Conversely, expression of the phospho-mimic NIRE1Y109E results in the formation of spontaneous nodules in L. japonicus, further emphasizing the critical role of the phosphorylation-dependent functional switch in NIRE1. In summary, these findings uncover a fine-tuned symbiotic mechanism that a single E3 ligase could undergo a phosphorylation-dependent functional switch to dynamically and precisely regulate NF receptor protein levels.

Pharmacokinetics and metabolites of glycosides and lignans of the stem bark of Magnolia officinalis in functional dyspepsia and normal rats using liquid chromatography-tandem mass spectrometry.

The stem bark of Magnolia officinalis is a traditional Chinese medicine for the treatment of abdominal distention and functional dyspepsia. The pharmacokinetics of three glycosides (magnoloside A, magnoloside B, and syringin) and two lignans (honokiol and magnolol) in both normal and functional dyspepsia rats were firstly investigated by ultra-performance liquid chromatography-triple quadrupole mass spectrometry method and the influences of the coexisting compounds on the pharmacokinetic parameters of honokiol and magnolol were also studied. It was found that all of the five target compounds were quickly absorbed and eliminated in both normal and functional dyspepsia rats, while, their residence time was significantly decreased in pathological states except magnoloside A. The coexisting compounds in the stem bark of M. officinalis significantly reduced absorption and increased elimination of honokiol in vivo. It's worth noticing that the volume of distribution of lignan was quite lower than that of a glycoside. Moreover, the metabolic profiling of magnoloside A, honokiol, and magnolol in vivo was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method, from which three prototypes were identified and 35 metabolites were putatively characterized, and 18 unknown metabolites were reasonably characterized for the first time. The results indicated that sulfation and glucuronidation were the main metabolic pathways of honokiol and magnolol.

Modulation of Brain Rhythm Oscillations by Xingnao Kaiqiao Acupuncture Correlates with Stroke Recovery: A Randomized Control Trial.

Objectives: In China, Xingnao Kaiqiao (XNKQ) acupuncture has been widely used for stroke treatment. However, its electrophysiological mechanism remains unclear. Hence, this study aims to study how XNKQ acupuncture modulates brain rhythm oscillations of stroke patients, and investigate its correlation with stroke recovery. Design: Randomized control trial. Subjects: Twenty (sub)acute ischemic stroke patients were enrolled and randomly assigned to two groups (an acupuncture group [AG] [n = 10] and a control group [CG] [n = 10]), and four patients (two patients in each group) dropped out of the study. Interventions: All patients received conventional treatments, and the patients in AG received additional XNKQ acupuncture treatment once a day for 10 consecutive days. Outcome measures: Before treatment, 14 days after, and 30 days after treatment onset, their movement impairments and neurologic deficits were measured using the National Institute of Health Stroke Scale (NIHSS), the Fugl-Meyer (FM) Scale, the Modified Rankin Scale (mRS), and the Modified Barthel Index (MBI), and their electroencephalogram data were recorded. Results: Compared with the CG, the AG showed more improvement in FM scores (p = 0.02), as well as decreased relative delta power and increased relative alpha power after 2 weeks' treatment. The decrease of the relative delta power and the increase of the relative alpha power in the ipsilesional frontal area were significantly correlated with the FM improvement (F5, F7, FC1, and Fz electrodes, all |r| > 0.517, p < 0.040). Conclusions: The curative effect of XNKQ acupuncture related to its electrophysiological modulation. This study was registered at the Chinese Clinical Trial Registry (ChiCTR2000038560).

Synergistic Inhibition of MRSA by Chenodeoxycholic Acid and Carbapenem Antibiotics.

Methicillin-resistant Staphylococcus aureus (MRSA) has posed a severe global health threat. In this study, we screened an antibiotic and non-antibiotic combination that provides a viable strategy to solve this issue by broadening the antimicrobial spectrum. We found that chenodeoxycholic acid (CDCA) could synergistically act with carbapenem antibiotics to eradicate MRSA-related infections. This synergy specifically targets MRSA and was also validated using 25 clinical MRSA strains using time-kill analysis. We speculated that the underlying mechanism was associated with the interaction of penicillin-binding proteins (PBPs). As a result, the synergistic efficiency of CDCA with carbapenems targeting PBP1 was better than that of ß-lactams targeting PBPs. Moreover, we showed that CDCA did not affect the expression level of PBPs, but sensitized MRSA to carbapenems by disrupting the cell membrane. In our study, we have revealed a novel synergistic combination of antibiotics and non-antibiotics to combat potential bacterial infections.

Screening active ingredients of rosemary based on spectrum-effect relationships between UPLC fingerprint and vasorelaxant activity using three chemometrics.

Rosmarinus officinalis L., rosemary, is traditionally used to treat headache and improve cardiovascular disease partly due to its vasorelaxant activity, while the vasorelaxant ingredients remain unclear. In this study, chemical spectrum-pharmacological effect relationship (spectrum-effect relationship) was utilized for efficiently discovering the main vasorelaxant ingredients of rosemary. Ten kinds of rosemary extracts were prepared by different extracting solvents and macroporous resin purification, and their chemical components were analyzed by UPLC. At the same time, the vasorelaxant activities of the 10 kinds of rosemary extracts were estimated on isolated rat thoracic aorta, and three chemometrics named partial least squares regression (PLSR), grey correlation analysis (GRA), and the least absolute shrinkage and selection operator (LASSO) were applied to construct spectrum-effect relationship between the UPLC fingerprints and vasorelaxant activity of rosemary extracts. As a result, most rosemary extracts showed dose-dependent increase in vasorelaxant activity and five kinds of ingredients, including carnosol, carnosic acid, epirosmanol methyl ether, carnosol isomer, and augustic acid were screened as vasorelaxant ingredients. Further, the vasorelaxant activities of carnosic acid and carnosol were verified. Moreover, the increase of nitric oxide (NO) and the decrease of angiotensin-II (Ang-II) were thought to contribute to the vasorelaxant activity of rosemary.

[Quality assessment of commercial rosemary based on liquid/gas chromatography and mass spectrography with multivariate statistical analysis].

A GC-MS fingerprint of rosemary oil and an UPLC fingerprint of non-volatile compounds of rosemary were established. Sixty-three kinds of volatile compounds and thirty-eight kinds of non-volatile compounds were identified tentatively using GC-MS and UPLC-Q-TOF-MS, respectively, and most of them are flavonoids, oxygenated monoterpenes, and diterpenoids, etc. According to multivariate data analysis, chemical differences existed among commercial rosemary samples, for example, the essential oil of imported rosemary sample belongs to Morocco/Tunisian type and the one of domestic sample belongs to Spanish type. The results of principal components analysis and partial least squares discriminant analysis showed that the imported and domestic rosemary samples were classified into two groups and fourteen components including eucalyptol, (+)-α-pinene, and carnosic acid, were found as the discrimination markers. In comparison with imported rosemary, it can be found that the contents of ten markers such as (+)-α-pinene, o-cymene, and carnosic acid were higher, nonetheless, lower contents for the other markers, in those domestic rosemary samples. Moreover, rosmarinic acid, an important bioactive component in rosemary extract, extensively varied among different samples, indicating that the quality evaluation of rosemary should be concerned.

Application of NIR and MIR spectroscopy for rapid determination of antioxidant activity of Radix Scutellariae from different geographical regions.

INTRODUCTION: The beneficial health effects of traditional Chinese medicines are often attributed to their potent antioxidant activities, usually established in vitro. However, these wet chemical methods for determining antioxidant activities are time-consuming, laborious, and expensive. OBJECTIVES: This study was conducted to establish a rapid determination of antioxidant activity of Radix Scutellariae using near-infrared (NIR) and mid-infrared (MIR) spectroscopy. MATERIAL AND METHODS: Antioxidant capabilities were evaluated using 2,2-diphenyl-1-picrylhydrazyl hydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays. The total flavonoid contents (TFCs) of Radix Scutellariae were measured by the aluminium chloride colorimetric method. The same sample was then scanned using NIR and MIR spectroscopy. Chemometrics analysis using partial least-squares (PLS) regression was performed to establish the models for predicting the antioxidant activities of Radix Scutellariae. RESULTS: A better predictive performance was achieved using PLS models based on NIR data. The determination coefficient (R(2)) and the residual predictive deviation (RPD) for the validation set were 0.9298 and 2.84 for DPPH, and 0.9436 and 2.66 for TFCs, respectively. MIR-PLS algorithms gave a slightly lower reliability (R(2) = 0.9090 and 0.9374, RPD = 2.01 and 2.42, for DPPH and TFC, respectively). Very comparable results for ORAC were obtained with the two methods. CONCLUSION: The developed spectroscopic method can be successfully applied in high-throughput screening of the antioxidant capability of Radix Scutellariae samples. It can also be a viable and advantageous alternative to laborious chemical procedures.

[Optimization of Aqueous Two-Phase Extraction of Polysaccharide from Schisandra chinensis Using Response Surface Methodology with Box-Behnken Design].

Objective: To optimize the extraction condition of polysaccharide from Schisandra chinensis. Aqueous two-phase extraction（ ATPE） method was used, based on Box-Behnken design with Response surface methodology（ BBD-RSM）. Methods: solvent volume,K2HPO4 and PEG6000 were selected as the investigation factors by the single-factor experiment, and the overall desirability（ OD）of phase volume ratio, partition coefficient and extraction rates were the reponse value. BBD-RSM was used to optimize the extraction process. . Results: The optimal parameters were as follows,the solvent volume was 5 m L,the addition amount of K2HPO4 was 1. 0 g, the addition amount of PEG6000 was 1. 8 g and centrifugation time was 9 min, which indicated that the model had a good predictability. The predicted value was 0. 950,and the deviation between observed and predicted values was 3. 94% Conclusion: The ATPE technology is easy to operate and cost-effective for the extraction of polysaccharides from Schisandra chinensis.