A Principal Component Regression-Based Electrophysiological Study of Patients with Severe Infections.

Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.

Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation.

Objective: The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR. Methods: The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results: In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms. Conclusions: Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study.

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged -7.09-11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

Quanzhen Yiqi decoction attenuates inflammation in mice with smoking-induced COPD by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome.

OBJECTIVE: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease. METHODS: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1ß/IL-18. RESULTS: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1ß and IL-18. CONCLUSION: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.

In-depth analysis of the treatment effect and synergistic mechanism of TanReQing injection on clinical multi-drug resistant Pseudomonas aeruginosa.

Antibiotic resistance is a recognized and concerning public health issue. Gram-negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), are notorious for their rapid development of drug resistance, leading to treatment failures. TanReQing injection (TRQ) was chosen to explore its pharmacological mechanisms against clinical multidrug-resistant P. aeruginosa (MDR-PA), given its antibacterial and anti-inflammatory properties. We revealed the expression of proteins and genes in P. aeruginosa after co-culture with TRQ. This study developed an assessment method to evaluate clinical resistance of P. aeruginosa using MALDI-TOF MS identification and Biotyper database searching techniques. Additionally, it combined MIC determination to investigate changes in MDR-PA treated by TRQ. TRQ effectively reduced the MICs of ceftazidime and cefoperazone and enhanced the confidence scores of MDR-PA as identified by mass spectrometry. Using this evaluation method, the fingerprints of standard P. aeruginosa and MDR-PA were compared, and the characteristic peptide sequence (Seq-PA No. 1) associated with flagellum was found. The phenotypic experiments were conducted to confirm the effect of TRQ on the motility and adhesion of P. aeruginosa. A combination of co-immunoprecipitation and proteome analysis was employed, and 16 proteins were significantly differentially expressed and identified as potential candidates for investigating the mechanism of inhibiting resistance in P. aeruginosa treated by TRQ. The candidates were verified by quantitative real-time PCR analysis, and TRQ may affect these core proteins (MexA, MexB, OprM, OprF, OTCase, IDH, and ASL) that influence resistance of P. aeruginosa. The combination of multiple methods helps elucidate the synergistic mechanism of TRQ in overcoming resistance of P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen closely associated with various life-threatening acute and chronic infections. The presence of antimicrobial resistance and multidrug resistance in P. aeruginosa infections significantly complicates antibiotic treatment. The expression of ß-lactamase, efflux systems such as MexAB-OprM, and outer membrane permeability are considered to have the greatest impact on the sensitivity of P. aeruginosa. The study used a method to assess the clinical resistance of P. aeruginosa using matrix-assisted laser desorption ionization time of flight mass spectrometry identification and Biotyper database search techniques. TanReQing injection (TRQ) effectively reduced the MICs of ceftazidime and cefoperazone in multidrug-resistant P. aeruginosa (MDR-PA) and improved the confidence scores for co-cultured MDR-PA. The study found a characteristic peptide sequence for distinguishing whether P. aeruginosa is resistant. Through co-immunoprecipitation and proteome analysis, we explored the mechanism of TRQ overcoming resistance of P. aeruginosa.

Two novel freshwater hyphomycetes, in Acrogenospora (Minutisphaerales, Dothideomycetes) and Conioscypha (Conioscyphales, Sordariomycetes) from Southwestern China.

Freshwater fungi are highly diverse in China and frequently reported from submerged wood, freshwater insects, herbaceous substrates, sediments, leaves, foams, and living plants. In this study, we investigated two freshwater species that were collected from Yunnan and Guizhou provinces in China. Detailed morphological analysis complemented by multi-gene phylogenetic analyses based on LSU, SSU, ITS, RPB2 and TEF1-α sequences data revealed them to be two new saprobic species, namely Acrogenosporaalangiisp. nov. and Conioscyphayunnanensissp. nov. in their asexual morphs. Additionally, Acrogenosporaalangiisp. nov. is reported for the first time as a freshwater ascomycete associated with the medicinal plant Alangiumchinense (Alangiaceae). Detailed morphological descriptions, illustrations and updated phylogenetic relationships of the new taxa are provided herein.

Mesoporous carbon nanoparticles embedded with iron in hydrogen-photothermal synergistic therapy.

We developed a new method to synthesize polyethylene glycol modified ultra small iron embedded in mesoporous carbon nanoparticle (C/Fe-PEG NP) for hydrogen (H2) assisted photothermal synergistic therapy. Herein, we use a simple in-situ reduction method to obtain the C/Fe NP in one-step carbonizing process, which is further modified by the biocompatible polyethylene glycol (PEG) on the surface of C/Fe NP to acquire high stability in physiological solutions. Utilizing the excellent photothermal property from the mesoporous carbon and the controllable H2 release property in the weakly acidic tumor microenvironment by the ultra-small Fe, the obtained C/Fe-PEG NPs can effective kill the cancer cells, meanwhile, protect normal cells without drugs. This selective anti-cancer mechanism of C/Fe-PEG NPs may because the produced H2 selective change the mitochondrial energy metabolism. In vivo results prove that the C/Fe-PEG NPs achieve excellent tumor ablation therapeutic effect and normal tissue protecting ability benefit from the H2-assisted photothermal therapy, promising the use of novel nanomaterials with more safety method for future cancer therapy.

Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. METHODS/DESIGN: This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography-mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. DISCUSSION: This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. ETHICS AND DISSEMINATION: Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. TRIAL REGISTRATION: ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Virus-like Particle Vaccines of Infectious Bursal Disease Virus Expressed in Escherichia coli Are Highly Immunogenic and Protect against Virulent Strain.

OBJECTIVES: Infectious bursal disease virus (IBDV) is a highly contagious, acutely infectious agent that causes immunosuppression in chickens. We expressed IBDV VP2 proteins in Escherichia coli (E. coli) to develop an effective virus-like-particles (VLPs) vaccine and evaluated its immunogenicity. METHODS: The VLPs produced in E. coli were used as an immunogen mixed with a water-in-mineral-oil adjuvant (MontanideTM ISA 71 VG, ISA 71 RVG) or a white oil (7#) adjuvant. VLPs without an adjuvant, commercial subunit vaccine, inactivated vaccine, and attenuated vaccine were used as controls. These test vaccines were intramuscularly injected into 19-day-old SPF chickens, which were challenged with the IBDV virulent strain at 30 days after vaccination. RESULTS: The adjuvants boosted antibody production, and the adjuvant groups (except white oil) produced higher antibody levels than the non-adjuvanted controls and the commercial vaccine groups. In terms of cellular immunity, the VLPs plus adjuvant combinations produced higher levels of cytokines, IL-2, IL-4, and IFN-γ than the controls. CONCLUSION: IBDV VLPs plus the ISA 71 RVG adjuvant can be used as an optimal vaccine combination for improving the immune efficacy of IBD subunit vaccines, which can protect against the virulent strain.

Diagnostic Significance of DCE-MRI-Related Quantitative Parameters for Nasal Cavity and Sinus Tumors.

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

Effects of maize and soybean intercropping on soil phosphorus bioavailability and microbial community structure in rhizosphere.

To investigate the effect of maize/soybean intercropping on rhizosphere soil microbial communities and phosphorus (P) bioavailability, we examined the changes of soil bioavailable P fractions and microbial community characteristics in the monoculture and intercropping systems based on high-throughput sequencing. The results showed that maize/soybean intercropping increased the contents of rhizosphere soil organic matter (SOM), available phosphorus (AP), microbial biomass phosphorus (MBP), and aboveground biomass. The increase of AP was mainly related to the increasing enzyme extracted phosphorus (Enzyme-P) and hydrochloric acid extracted phosphorus (HCl-P) contents. The dominant bacterial phyla under each treatment were Proteobacteria, Actinobacteria, Acidobacteria and Chloroflexi, while the dominant bacterial genera were Nocardioides, Solirubacter, Sphingomonas and Arthrobacter, with Proteobacteria and Sphingomonas having the highest relative abundance. The relative abundance of Proteobacteria and Sphingomonas in intercropping maize rhizosphere soil was significantly higher than that in monoculture, and that of Proteobacteria in intercropping soybean rhizosphere soil was significantly higher than monoculture. Soil properties and P fractions were closely related to the rhizosphere soil microbial composition. In all, maize/soybean intercropping could affect the rhizosphere soil P bioavailability by altering the structure of rhizosphere microbial communities.

Does Flavonoid Supplementation Alleviate Non-Alcoholic Fatty Liver Disease? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

SCOPE: Higher flavonoid intake is associated with reduced risk of non-alcoholic fatty liver disease (NAFLD). However, there is a large discrepancy in the effects of flavonoid supplementation on NAFLD. To fill such knowledge gap, we systematically reviewed randomized clinical trials (RCTs) to critically assess flavonoid supplementation effect on liver function, lipid profile, inflammation, and insulin resistance in adults with NAFLD. METHODS AND RESULTS: A systematic search was conducted from 4 databases from inception until May 2023. Twelve RCTs were included in the final analysis demonstrating beneficial effects of flavonoids on ALT (SMD = -3.59, p = 0.034), AST (SMD = -4.47, p = 0.001), GGT (SMD = -8.70, p = 0.000), CK-18M30 (SMD = -0.35, p = 0.042), TG (SMD = -0.37, p = 0.001), LDL-C (SMD = -0.38, p = 0.039), TC (MD = -0.25 mmol/l, p = 0.017), steatosis score (MD = -18.97, p = 0.30), TNF-α (MD = -0.88, p = 0.000), and NF-κB (MD = -1.62, p = 0.001). CONCLUSION: This meta-analysis suggests that flavonoid alleviates NAFLD through exerting favourable effects on liver function, lipid profile, and inflammation, indicating flavonoid supplementation presents a promising drug regimen for the management of NAFLD and its associated complications.

Growth hormone supplementation during ovarian stimulation in women with advanced maternal age undergoing preimplantation genetic testing for Aneuploidy.

BACKGROUND: Studies have shown that supplementation with recombinant human GH (rh-GH) during ovarian stimulation (OS) may improve the ovarian response and clinical outcomes of IVF. However, it remains unclear whether GH is associated with the ploidy status of embryos, and therefore, is unable to explain the underlying reason for the effect of GH on IVF outcomes. This study aimed to investigate whether GH supplementation in women with advanced maternal age (AMA) during OS is related to an increased probability of obtaining euploid blastocysts. METHODS: This was a single center retrospective cohort study. The data of all women aged 38-46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle between January 2021 and June 2022 were reviewed. Patients in the GH group received 4 IU/day subcutaneous GH supplementation from the beginning of OS to the trigger day, and patients in the control group did not. A total of 140 patients in the GH group and 272 patients in the control group were included after 1:2 propensity score matching. RESULTS: The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group than that in the control group (41.43% vs. 27.21%, P = 0.00). The GH group had a significantly higher euploid blastocyst rate per cohort (32.47% vs. 21.34%, P = 0.00) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.35 ± 0.40 vs. 0.21 ± 0.33, P = 0.00; per OS cycle 0.27 ± 0.38 vs. 0.16 ± 0.30, P = 0.02). However, the benefit of GH was more significant in patients aged 38-40 years, but not significant in patients aged 41-46 years. Pregnancy outcomes were similar between the two groups after embryo transfer. CONCLUSIONS: GH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38-40 years, but this benefit is not significant in women aged 41-46 years. Our results explained the underlying reason for the effect of GH on IVF outcomes in existing studies, and might be helpful for AMA patients undergoing PGT-A cycles to obtain a better outcome meanwhile to avoid over-treatment. TRIAL REGISTRATION: NCT05574894, www. CLINICALTRIALS: gov .

Metagenomics, metatranscriptomics, and proteomics reveal the metabolic mechanism of biofilm sequencing batch reactor with higher phosphate enrichment capacity under low phosphorus load.

The biofilm sequencing batch reactor (BSBR) process has higher phosphate recovery efficiency and enrichment multiple when the phosphorus load is lower, but the mechanism of phosphate enrichment at low phosphorus load remains unclear. In this study, we operated two BSBR operating under low and high phosphorus load (0.012 and 0.032 kg/(m3·d)) respectively, and used metagenomic, metatranscriptomic, and proteomics methods to analyze the community structure of the phosphorus accumulating organisms (PAOs) in the biofilm, the transcription and protein expression of key functional genes and enzymes, and the metabolism of intracellular polymers. Compared with at high phosphorus load, the BSBR at low phosphorus load have different PAOs and fewer types of PAOs, but in both cases the PAOs must have the PHA, PPX, Pst, and acs genes to become dominant. Some key differences in the metabolism of PAOs from the BSBR with different phosphorus load can be identified as follows. When the phosphorus load is low, the adenosine triphosphoric acid (ATP) and NAD(P)H in the anaerobic stage come from the TCA cycle and the second half of the EMP pathway. The key genes that are upregulated include GAPDH, PGK, ENO, ppdk in the EMP pathway, actP in acetate metabolism, phnB in polyhydroxybutyrate (PHB) synthesis, and aceA, mdh, sdhA, and IDH1 in the TCA cycle. In the meantime, the ccr gene in the PHV pathway is inhibited. As a result, the metabolism of the PAOs features low glycogen with high PHB, Pupt, Prel, and low PHV. That is, more ATP and NAD(P)H flow to phosphorus enrichment metabolism, thus allowing the highly efficient enrichment of phosphorus from low concentration phosphate thanks to the higher abundance of PAOs. The current results provide theoretical support and a new technical option for the enrichment and recovery of low concentrations of phosphate from wastewater by the BSBR process.

Selenium inhibits ferroptosis in hyperglycemic cerebral ischemia/reperfusion injury by stimulating the Hippo pathway.

Hyperglycemia can exacerbate cerebral ischemia/reperfusion (I/R) injury, and the mechanism involves oxidative stress, apoptosis, autophagy and mitochondrial function. Our previous research showed that selenium (Se) could alleviate this injury. The aim of this study was to examine how selenium alleviates hyperglycemia-mediated exacerbation of cerebral I/R injury by regulating ferroptosis. Middle cerebral artery occlusion (MCAO) and reperfusion models were established in rats under hyperglycemic conditions. An in vitro model of hyperglycemic cerebral I/R injury was created with oxygen-glucose deprivation and reoxygenation (OGD/R) and high glucose was employed. The results showed that hyperglycemia exacerbated cerebral I/R injury, and sodium selenite pretreatment decreased infarct volume, edema and neuronal damage in the cortical penumbra. Moreover, sodium selenite pretreatment increased the survival rate of HT22 cells under OGD/R and high glucose conditions. Pretreatment with sodium selenite reduced the hyperglycemia mediated enhancement of ferroptosis. Furthermore, we observed that pretreatment with sodium selenite increased YAP and TAZ levels in the cytoplasm while decreasing YAP and TAZ levels in the nucleus. The Hippo pathway inhibitor XMU-MP-1 eliminated the inhibitory effect of sodium selenite on ferroptosis. The findings suggest that pretreatment with sodium selenite can regulate ferroptosis by activating the Hippo pathway, and minimize hyperglycemia-mediated exacerbation of cerebral I/R injury.

Developmental neurotoxicity evaluation of three Chinese herbal medicines in zebrafish larvae by means of two behavioral assays: Touch-evoked response and light/dark transition.

Chinese herbal medicine (CHM) is used among pregnant women. However, the question of its safety during pregnancy remains unclear. The use of these products relies on history of use data but there are specific toxicities like developmental neurotoxicity that are clearly understudied. Here we use the zebfrafish embryo developmental toxicity assay (ZEDTA) in combination with two behavioral assays: touch-evoked response and Light/Dark (L/D) transition assay to evaluate the neuro/developmental toxicity of three herbal products commonly used in CHM [Chinese name (abbreviation; part of the plant and Scientific name]: tian ma (TM; tuber form Gastrodia elata Blume), lei gong teng (LGT; root and rhizome of Tripterygium wilfordii Hook.f) and cha ye (green tea, leaves from Camellia sinensis (L.) Kuntze). In case significant alterations were detected, single components with potential exposure during pregnancy were identified in the literature and further tested. TM had no neurodevelopmental toxic potential in zebrafish embryos, while LGT and its main compounds triptolide and celastrol induced significant alterations in behavior. Developmental exposure to EGCG, the main catechin of green tea, also produced significant alterations in zebrafish embryos behavior after developmental exposure. A combination of ZEDTA with L/D Transition assay is proposed as a useful combination of alternative methods for DNT assessment of CHM products together with other New Approach Methodologies (NAMs).

In vitro bloodbrain barrier permeability study of four main active ingredients from Alpiniae oxyphyllae fructus.

The fruits of Alpinia oxyphylla Miq., a broadly utilized traditional Chinese medicine, have a number of effects on the central nervous system (CNS). The main active constituents of Alpiniae oxyphyllae fructus (AOF) were nootkatone, tectochrysin, chrysin and protocatechuic acid. An immortalized human brain microvascular endothelial cell (hCMEC/D3) and astrocyte (HA1800) coculture model was used to investigate the permeability of the blood-brain barrier (BBB). The validation of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods for the four compounds was conducted following industry guidelines. Calibration curves were generated with mean coefficients (R2) better than 0.99. The inter-day and intra-day precisions were less than 8.53% and 7.12%, respectively. The accuracies were lower than ± 11.57%, and recoveries were greater than 86.07%. The samples of the transport experiment were examined, and the apparent permeability coefficients (Papp) were calculated. The efflux ratios of the four compounds are all less than 2. The Papp values of protocatechuic acid, chrysin, nootkatone, tectochrysin were at the level of 10-5, 10-6, 10-6, and 10-7 cm/s, respectively. All four compounds crossed the BBB by passive diffusion, with protocatechuic acid having high permeability, and tectochrysin having poor permeability. This research indicated the permeability of protocatechuic acid, chrysin, nootkatone and tectochrysin through the BBB and offered a foundation for related research on AOF in the treatment of CNS illnesses.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Insight into the medium-long-medium structured lipids made from Camellia oil: Composition-structure relationship.

Medium-long-medium (MLM) structured lipid (SL) as a new SL is a potential functional ingredient in food and nutraceutical products, but its composition-structure-physicochemical properties relationship has not been revealed in food industry. MLM type of medium-long chain triacylglycerol (MLCT) was synthesized from Camellia oil by combi-lipase; its physicochemical properties and composition-structure relationship were investigated in this research. The higher MLCT (67.24% ± 0.09) and MLM (52.71% ± 0.53) productivities were achieved after parameter optimization. The physicochemical characterization of SLs exhibited mild thermal property, intermediate Fourier transform infrared spectroscopy absorption intensity, and better crystal morphology. Joint characterizations identified that MLM and long-medium-long type SL were rich in 1,3-dioctanoyl-2-linoleoyl glyceride (CaLCa), 1,3-dioctanoyl-2-oleoyl glyceride (CaOCa), 1,3-dilinoleoyl-2-octanoyl glyceride (LCaL), and 1,3-dilinoleoyl-2-decanoyl glyceride (LCL) components, respectively. This is ascribed to the higher proportion of caprylic and linoleic acid in 1,3-specific enzyme. The 3D structural analysis further demonstrated that the CaLCa, CaOCa, LCaL, and LCL molecules had lower steric energy to form symmetrical structure at 1,3-position. This research provides a practical method to produce MLM-type SL from edible oils and fats in food industry.

Protective Effects of Selenium Nanoparticles against Bisphenol A-Induced Toxicity in Porcine Intestinal Epithelial Cells.

Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na2SeO3) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na2SeO3. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na2SeO3 treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na2SeO3 treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1ß(IL-1ß), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na2SeO3 can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na2SeO3 and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans.