Asymmetric response of aboveground and belowground temporal stability to nitrogen and phosphorus addition in a Tibetan alpine grassland.

Anthropogenic eutrophication is known to impair the stability of aboveground net primary productivity (ANPP), but its effects on the stability of belowground (BNPP) and total (TNPP) net primary productivity remain poorly understood. Based on a nitrogen and phosphorus addition experiment in a Tibetan alpine grassland, we show that nitrogen addition had little impact on the temporal stability of ANPP, BNPP, and TNPP, whereas phosphorus addition reduced the temporal stability of BNPP and TNPP, but not ANPP. Significant interactive effects of nitrogen and phosphorus addition were observed on the stability of ANPP because of the opposite phosphorus effects under ambient and enriched nitrogen conditions. We found that the stability of TNPP was primarily driven by that of BNPP rather than that of ANPP. The responses of BNPP stability cannot be predicted by those of ANPP stability, as the variations in responses of ANPP and BNPP to enriched nutrient, with ANPP increased while BNPP remained unaffected, resulted in asymmetric responses in their stability. The dynamics of grasses, the most abundant plant functional group, instead of community species diversity, largely contributed to the ANPP stability. Under the enriched nutrient condition, the synchronization of grasses reduced the grass stability, while the latter had a significant but weak negative impact on the BNPP stability. These findings challenge the prevalent view that species diversity regulates the responses of ecosystem stability to nutrient enrichment. Our findings also suggest that the ecological consequences of nutrient enrichment on ecosystem stability cannot be accurately predicted from the responses of aboveground components and highlight the need for a better understanding of the belowground ecosystem dynamics.

Novel magnetic graphoxide/biochar composite derived from tea for multiple SAs and QNs antibiotics removal in water.

Antibiotics pollution is an urgent public health issue. Biochar is a kind of promising composite for removal antibiotic in aqueous environment. In this study, a novel magnetic graphoxide/biochar composite (mGO/TBC) was synthesized by simple impregnation method and used as an efficient and recyclable persulfate (PS) activator for degradation and removal of sulfonamides (SAs) and quinolones (QNs) antibiotics. Based on the synergism pre-adsorption and degradation between graphoxide and biochar, the removal rates of mGO/TBC on sarafloxacin hydrochloride, sulfadimethoxine, sulfapyridine, sulfadoxine, sulfamonomethoxine, sulfachloropyridazine, enrofloxacin, and ciprofloxacin were increased above 95%. Moreover, the mGO/TBC could be reused at least seven times after degradation-recovery cycles. Quenching experiment and ESR analysis proved that 1O2, •OH, and SO4•- from mGO/TBC/PS system were the primary oxidation active species to degrade SAs and QNs. It is a promising substrate for antibiotic bioremediation with good application prospects.

Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening.

Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 infection was investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosis and secreting inflammatory factors such as IL-1ß. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing infection time, and USA300 induces mPEOs to undergo pyroptosis and autophagy. In addition, we performed a drug screen for the mPEO infection model and showed that vancomycin restores cell viability and inhibits bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.

Transcutaneous Electrical Acupoint Stimulation Combined With Auricular Acupressure Reduces Postoperative Delirium Among Elderly Patients Following Major Abdominal Surgery: A Randomized Clinical Trial.

Background: Postoperative delirium is common in elderly patients following major surgery. This study aimed to assess the effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on the incidence of postoperative delirium among older patients undergoing major abdominal surgery. Methods: In this single-center, randomized controlled clinical trial, 210 patients aged 65 years or older undergoing major abdominal surgery were randomized to receive either intervention treatment (transcutaneous electrical acupoint stimulation started at 30 min before anesthesia until the end of the surgery, followed by intermittent auricular acupressure in the first three postoperative days; n = 105) or standard care (n = 105). The primary outcome was the incidence of delirium at the first seven postoperative days or until hospitalization depended on which came first. Secondary outcomes included delirium severity, opioid consumption, postoperative pain score, sleep quality, length of postoperative hospital stay, and postoperative 30-day complications. Enrollment was from April 2019 to March 2020, with follow-up ending in April 2020. Results: All of the 210 randomized patients [median age, 69.5 years, 142 (67.6%) male] completed the trial. The incidence of postoperative delirium was significantly reduced in patients received intervention treatment (19/105 (18.1%) vs. 8/105 (7.6%), difference, -10.5% [95% CI, -1.5% to -19.4%]; hazard ratio, 0.41 [95% CI, 0.18 to 0.95]; P= 0.023). Patients in the control group had a higher postoperative Memorial Delirium Assessment Scale (4 vs. 3; difference, -1; 95% CI, -1 to 0; P = 0.014) and a greater increase in Pittsburgh Sleep Quality Index score from baseline to postoperative day three (2.5 vs. 2.0; difference, -1; 95% CI, -2 to -1; P < 0.001) than patients in the intervention group. No significant difference was observed as of other secondary outcomes. Conclusion: In elderly patients undergoing major abdominal surgery, transcutaneous electrical acupoint stimulation combined with auricular acupressure reduced the incidence of postoperative in-hospital delirium compared with standard care. A multicenter, randomized clinical trial with a larger sample size is necessary to verify these findings. Clinical Trial Registration: [https://clinicaltrials.gov], identifier [NCT03726073].

A Comprehensive Review of Lipidomics and Its Application to Assess Food Obtained from Farm Animals.

Lipids are one of the major macronutrients essential for adequate growth and maintenance of human health. Their structure is not only complex but also diverse, which makes systematic and holistic analyses challenging; consequently, little is known regarding the relationship between phenotype and mechanism of action. In recent years, rapid advancements have been made in the fields of lipidomics and bioinformatics. In comparison with traditional approaches, mass spectrometry-based lipidomics can rapidly identify as well as quantify >1,000 lipid species at the same time, facilitating comprehensive, robust analyses of lipids in tissues, cells, and body fluids. Accordingly, lipidomics is now being widely applied in various fields, particularly food and nutrition science. In this review, we discuss lipid classification, extraction techniques, and detection and analysis using lipidomics. We also cover how lipidomics is being used to assess food obtained from livestock and poultry. The information included herein should serve as a reference to determine how to characterize lipids in animal food samples, enhancing our understanding of the application of lipidomics in the field in animal husbandry.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

Transcriptome Atlas of 16 Donkey Tissues.

Donkeys (Equus asinus) are important livestock with great economic value in meat, skin, and milk production. However, a lack of knowledge of the transcriptome landscape across a wide range of donkey tissues limits genetic selective breeding and conservation. Here we used transcriptomics to describe the transcriptome landscape, classify the tissue-specific gene expression across all primary donkey tissues, and present supplementary analyses on the protein level of additional donkey milk samples. Overall, 16,013 protein-coding genes and 21,983 transcripts were mapped to the reference genome, including 6,778 ubiquitously expressed genes and 2,601 tissue-enriched genes. Functional analysis revealed that the function of the tissue-enriched genes was highly tissue specific. Tissue-elevated genes that could be associated with unique phenotypes in donkey were analyzed. The results showed that, compared with those in human and other livestock, the lysozyme gene in donkey breast was specifically and highly expressed. The calcium-binding lysozyme, encoded by the lysozyme gene, was also detected in high amounts in donkey milk. Given those intact lysozyme genes that predict potentially functional calcium-binding lysozyme found in only a few species (e.g., donkey and horse), the high expression of the lysozyme gene in donkey breast may contribute to the high lysozyme content in donkey milk. Furthermore, 71% of the proteins in donkey milk overlapped with human milk protein, higher than the overlapping rates of bovine, sheep, and swine with humans. The donkey transcriptomic resource contributes to the available genomic resources to interpret the molecular mechanisms underlying phenotype traits.

Transcutaneous electrical acupoint stimulation before surgery reduces chronic pain after mastectomy: A randomized clinical trial.

STUDY OBJECTIVE: Despite multiple interventions, the incidence of chronic pain after mastectomy could be as high as 50% after surgery. This study aimed to determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) before anesthesia induction in reducing chronic pain and to compare the effect of combined acupoint TEAS with that of single acupoint TEAS. DESIGN: A multicenter randomized clinical trial. SETTING: The study was conducted at six medical centers in China from May 2016 to April 2018. Final follow-up was on October 26, 2018. PARTICIPANTS: Eligible patients were women scheduled for radical mastectomy under general anesthesia. INTERVENTIONS: Patients were randomly and equally grouped into sham control (n = 188), single acupoint (PC6, n = 198), or combined acupoints (PC6 and CV17, n = 190) TEAS groups using a centralized computer-generated randomization system. TEAS was applied for 30 min before anesthesia induction. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists, surgeons, and outcome assessors were blinded to the interventions. MEASURES: The primary endpoint was the incidence of chronic pain 6 months after surgery. Incidences were compared among the groups using the unadjusted χ2 test. RESULTS: Of the 576 randomized patients, 568 completed the trial. In the intention-to-treat analysis, post-mastectomy pain at 6 months was reported in 42 of 190 patients (22.1%) in the combined acupoints group, 65 of 188 patients (34.6%) in the sham-operated group (P = 0.007; relative risk [RR], 95% confidence interval [CI]: 0.68, 0.52-0.89), and 72 of 198 patients (36.4%) in the single acupoint group (P = 0.002; RR, 95% CI: 0.72, 0.55-0.93). Remifentanil consumption during surgery and postoperative nausea and vomiting at 24 h after surgery were lower in the combined acupoint group than that in the sham-operated group. CONCLUSION: TEAS at combined acupoints before surgery was associated with reduced chronic pain 6 months after surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02741726. Registered on April 13, 2016.

Efficacy and Safety Evaluation of Transurethral Resection of the Prostate versus Plasmakinetic Enucleation of the Prostate in the Treatment of Massive Benign Prostatic Hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common chronic progressive disease resulting in urinary obstruction in aging men. It comes to more and more patients with massive BPH with the aging of society and extension of life expectancy. OBJECTIVE: The aim of the study was to compare the clinical efficacy, safety, and complications between transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) and transurethral resection of the prostate (TURP) in the treatment of massive BPH. DESIGN AND SETTING: Patients with BPH were divided into the PKEP group and the TURP group randomly. Intraoperative blood loss (BL), operation time (OT), resected tissue weight (RTW), gland resection ratio (GRR), postoperative indwelling ureter time (IUT), bladder fistula time (BFT) and hospital stay time (HST), preoperative and postoperative serum sodium concentration (SSC), hemoglobin concentration (HGB), prostate weight (PW), postvoid residual (PVR), maximum urinary flow rate (Qmax), international prostate symptom score (IPSS), quality of life (QOL), International Index of Erectile Function (IIEF), and other complications were analyzed and compared respectively. RESULTS: There was no statistical difference in preoperative IPSS, preoperative QOL score, preoperative PVR, preoperative Qmax, postoperative QOL score, postoperative PVR, postoperative Qmax, IPSS difference value (DV), Qmax DV, and PVR DV between the PKEP group and the TURP group (p > 0.05). OT, BL, IUT, BFT, HST, and postoperative IPSS in the PKEP group were significantly lower than that in the TURP group (p < 0.01). RTW and GRR in the PKEP group were significantly higher than that in the TURP group (p < 0.01). QOL DV in the PKEP group was higher than that in the TURP group (p < 0.05). There was statistical difference in SSC DV between the PKEP group and the TURP group (p < 0.05). There was significant statistical difference in postoperative PW, postoperative HGB, PW DV, and HGB DV between the PKEP group and the TURP group (p < 0.01). There was significant statistical difference in IPSS, QOL, PVR, and Qmax between postoperative value and preoperative value in both groups (p < 0.01). The incidence of transurethral resection syndrome, obturator nerve reflex, transient urinary incontinence, and retrograde ejaculation between the PKEP group and the TURP group has no statistical difference (p > 0.05). Capsule perforation, blood transfusion, secondary hemorrhage, bladder neck contracture, and urethral stricture in the PKEP group were lower than that in the TURP group (p < 0.05). Bladder spasm in the PKEP group was significantly lower than that in the TURP group (p < 0.01). There was no statistical difference in preoperative and postoperative IIEF-5, effective erectile frequency, telotism average tension, sustainable telotism average time, and sexual dissatisfaction between the PKEP group and the TURP group (p > 0.05). CONCLUSIONS: PKEP and TURP have similar clinical efficacy in the treatment of massive BPH. PKEP has advantages in shorter OT, less BL, more GRR, and fewer complications, but the long-term therapeutic effect of PKEP needs further follow-up.

Efficacy and safety of prostatic artery embolization for benign prostatic hyperplasia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy and safety of prostatic artery embolization (PAE) vs. transurethral resection of the prostate (TURP) in patients affected by benign prostatic hyperplasia (BPH). We also reviewed mean changes from baseline in PAE at selected follow-up points. METHODS: PubMed, Web of Science, and Embase were searched up to May 1, 2020. Randomized controlled trials on PAE were collected according to specific inclusion and exclusion criteria. Meta-analyses were performed using RevMan 5.3, STATA 14, and GraphPad Prism 8. Pooled patient-reported scores and functional outcomes were calculated by using a fixed or random-effect model. RESULTS: Eleven articles met our selection criteria and ten independent patient series were included in the final analysis. Pooled estimates suggested no significant difference between TURP and PAE for patient-reported outcomes including International Prostate Symptom Score (2.32 (- 0.44 to 5.09)) and quality of life (0.18 (- 0.41 to 0.77)) at 12 months. PAE was less effective regarding improvements in most functional outcomes such as maximum flow rate, prostate volume, and prostate-specific antigen. Moreover, PAE may be associated with relatively fewer complications, lower cost, and shorter hospitalization. After the PAE procedure, the overall weighted mean differences for all outcomes except sexual health scores were significantly improved from baseline during follow-up to 24 months. CONCLUSION: PAE is non-inferior to TURP with regard to improving patient-reported outcomes, though most functional parameters undergo more changes after TURP than after PAE. Moreover, PAE can significantly continue to relieve symptoms for 24 months without causing serious complications. KEY POINTS: • PAE is as effective as TURP in improving subjective symptom scores, with fewer complications and shorter hospitalization times. • PAE is inferior to TURP in the improvement of most functional outcomes. • Improvements due to PAE are durable during follow-up to 24 months.

Comparison of Two Different Natural Oil Body Emulsions: in vitro Gastrointestinal Digestion.

The surface compositions and structure of oil bodies (OBs) are dependent on the oil crop, and these factors affect in vitro gastrointestinal digestion behaviors. Herein, a comparative study was conducted to examine the in vitro gastrointestinal digestion characteristics of two natural emulsions prepared with soybean seeds and rapeseed OBs during gastrointestinal digestion process. The average particle size of soybean OBs and rapeseed OBs emulsions was 0.46 and 5.02 µm, respectively. The droplet size of soybean seed and rapeseed OBs emulsions was large with relatively low zeta-potentials at 30 min digestion time in simulated gastric fluid condition. The droplet size of two natural OBs emulsions decreased with increasing digestion time in simulated gastric fluid condition. The average droplet size of both emulsions gradually decreased with increasing digestion time in simulated intestinal fluid conditions. The zeta-potential of the two emulsions increased with increasing digestion time in simulated intestinal fluid conditions. The extent of free fatty acids of soybean OBs emulsions was significantly higher than rapeseed after 20 min digestion time in simulated intestinal fluid conditions. The obtained results suggested that plant OBs could be useful as natural emulsifiers in the development of functional food and achieve controlled release of bioactive compounds from emulsions during gastrointestinal digestion.

[Anti-tumor effect and its related mechanisms of cinobufotalin combined with cisplatin on H22 liver cancer mice].

In order to observe the anti-tumor effect of cinobufotalin on H22 liver cancer mice and to explore its regulatory mechanism, 50 Kunming mice were subcutaneously inoculated with H22 intraperitoneal passage cells under the armpit to establish H22 hepatocellular carcinoma model. They were then randomly divided into model group, cinobufotalin low dose group, cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, which received 0.01% ethanol solution, 1 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cisplatin, 5 mg·kg~(-1)cisplatin + 5 mg·kg~(-1) cinobufotalin respectively for 10 days. The general condition of mice during the intervention was observed, and the inhibition rate, tumor mass, thymus index, histopathological changes of the tumors, apoptotic rate of the tumors, the expressions of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), apoptosis related gene(Fas), Fas ligand(FasL) mRNA and protein phosphorylated Akt(pAkt) protein in the tumors of each group were compared. The results showed that during the modeling period, the mice showed a decline in food intake, dark fur, poor mental status, and gradually worsened over time. The mental status of mice in each intervention group was improved gradually, especially in the cisplatin+cinobufotalin group. As compared with the model group, the tumor mass of each intervention group was lower(P<0.05). As compared with the cinobufotalin low dose group, the tumor mass was lower and inhibition rate was higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, the tumor mass was lower and the inhibition rate was higher in cisplatin+cinobufotalin group(P<0.05). As compared with the model group, the thymus index was higher in cinobufotalin high dose group and cisplatin + cinobufotalin group, while was lower in cisplatin group(P<0.05). As compared with the cinobufotalin low dose group, the thymus index was higher in the cinobufotalin high dose group and lower in the cisplatin group(P<0.05). As compared with the cinobufotalin high dose group, the thymus index was lower in cisplatin group(P<0.05). As compared with cisplatin group, the thymus index was higher in cisplatin+cinobufotalin group(P<0.05). Pathological staining showed that a large number of heterogeneous cells and mitotic phenomena were observed in the model group. Cell fragments and neutrophils were observed in the tumor tissues of the intervention groups, showing diffuse necrosis, and the diffuse necrosis was more obvious in the cisplatin+cinobufotalin group. As compared with the model group, the apoptotic rate of the tumors and the relative expressions of Fas mRNA and protein were higher in the intervention groups, while the relative expressions of PI3 K, FasL mRNA and protein and the relative expression of pAkt protein were lower in the intervention groups(P<0.05). As compared with the cinobufotalin low dose group, the apoptotic rate of the tumors and relative expression of Fas and protein were higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, apoptotic rate of the tumors and the relative expression of Fas mRNA and protein were higher in the cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower in the cisplatin+cinobufotalin group(P<0.05). In summary, cinobufotalin has significant anti-tumor effect on H22 liver cancer mice, and can enhance the immune function of mice and synergistically enhance the effect of chemotherapy. Its mechanism may be associated with regulating PI3 K/Akt/Fas/FasL signaling pathway related genes and protein expression.

Median Nerve Electrical Stimulation-Induced Changes in Effective Connectivity in Patients With Stroke as Assessed With Functional Near-Infrared Spectroscopy.

Background. The cortical plastic changes in response to median nerve electrical stimulation (MNES) in stroke patients have not been entirely illustrated. Objective. This study aimed to investigate MNES-related changes in effective connectivity (EC) within a cortical network after stroke by using functional near-infrared spectroscopy (fNIRS). Methods. The cerebral oxygenation signals in the bilateral prefrontal cortex (LPFC/RPFC), motor cortex (LMC/RMC), and occipital lobe (LOL/ROL) of 20 stroke patients with right hemiplegia were measured by fNIRS in 2 conditions: (1) resting state and (2) MNES applied to the right wrist. Coupling function together with dynamical Bayesian inference was used to assess MNES-related changes in EC among the cerebral low-frequency fluctuations. Results. Compared with the resting state, EC from LPFC and RPFC to LOL was significantly increased during the MNES state in stroke patients. Additionally, MNES triggered significantly higher coupling strengths from LMC and LOL to RPFC. The interregional main coupling direction was observed from LPFC to bilateral motor and occipital areas in responding to MNES, suggesting that MNES could promote the regulation function of ipsilesional prefrontal areas in the functional network. MNES can induce muscle twitch of the stroke-affected hand involving a decreased neural coupling of the contralesional motor area on the ipsilesional MC. Conclusions. MNES can trigger sensorimotor stimulations of the affected hand that sequentially involved functional reorganization of distant cortical areas after stroke. Investigating MNES-related changes in EC after stroke may help further our understanding of the neural mechanisms underlying MNES.

Triptolide, A Potential Autophagy Modulator.

As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.

Enzyme-assisted development of biofunctional polyphenol-enriched buckwheat protein: physicochemical properties, in vitro digestibility, and antioxidant activity.

BACKGROUND: During the last decade buckwheat was reported to have positive health effects. The present study investigated a high-polyphenol buckwheat protein (Fagopyrum esculentum Moench) prepared by enzyme-assisted processing, together with its physicochemical properties, in vitro digestibility, and antioxidant activity. RESULTS: Buckwheat protein prepared from the synergistic enzymatic action of α-amylase and amyloglucosidase (E-BWP) had much higher polyphenol content than buckwheat protein prepared by isoelectric precipitation (I-BWP) or salt extraction (S-BWP). Rutin degraded during the process, giving quercetin. The protein constituents and amino acid composition of E-BWP were very similar to those of native buckwheat and were able to meet the WHO/FAO requirements for both children and adults. During in vitro digestion, E-BWP showed anti-digestive behavior with a nitrogen release that was lower than that of I-BWP or S-BWP. The positive effect of the polyphenol content of E-BWP resulted in a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) content and greater reducing activity. CONCLUSION: Buckwheat protein with high polyphenol content was successfully developed by enzyme-assisted processing. It had a well-balanced amino acid profile, antidigestive behavior, and high antioxidant activities. The results suggest that enzyme-assisted processing is promising in the production of polyphenol-enriched cereal protein, contributing higher functionality with good nutritional and antioxidant properties. © 2018 Society of Chemical Industry.

Molecular Mechanism of Action of RORγt Agonists and Inverse Agonists: Insights from Molecular Dynamics Simulation.

As an attractive drug-target, retinoic acid receptor-related orphan receptor-gamma-t (RORγt) has been employed widely to develop clinically relevant small molecular modulators as potent therapy for autoimmune disease and cancer, but its molecular mechanism of action (MOA) remains unclear. In the present study, we designed and discovered two novel RORγt ligands that are similar in structure, but different in efficacy. Using fluorescence resonance energy transfer (FRET) assay, compound 1 was identified as an agonist with an EC50 of 3.7 µM (max. act.: 78%), while compound 2 as an inverse agonist with an IC50 value of 2.0 µM (max. inh.: 61%). We performed molecular dynamics (MD) simulations, and elucidated the MOA of RORγt agonist and inverse agonist. Through the analyses of our MD results, we found that, after RORγt is bound with the agonist 1, the side chain of Trp317 stays in the gauche- conformation, and thus helps to form the hydrogen bond, His479-Trp502, and a large hydrophobic network among H11, H11', and H12. All these interactions stabilize the H12, and helps the receptor recruit the coactivator. When the RORγt is bound with the inverse agonist 2, the side chain of Trp317 is forced to adopt the trans conformation, and these presumed interactions are partially destroyed. Taken together, the critical role of residue Trp317 could be viewed as the driving force for the activation of RORγt.

Effect of dual-acupoint and single-acupoint electric stimulation on postoperative outcomes in elderly patients subjected to gastrointestinal surgery: study protocol for a randomized controlled trial.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) has shown benefits when used peri-operatively. However, the role of numbers of areas with acupoint stimulation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using TEAS in elderly patients subjected to gastrointestinal surgery, and comparing dual-acupoint and single-acupoint stimulation. METHODS/DESIGN: A multicenter, randomized, controlled, three-arm design, large-scale trial is currently undergoing in four hospitals in China. Three hundred and forty-five participants are randomly assigned to three groups in a 1:1:1 ratio, receiving dual-acupoint TEAS, single-acupoint TEAS, and no stimulation, respectively. The primary outcome is incidence of pulmonary complications at 30 days after surgery. The secondary outcomes include the incidence of pulmonary complications at 3 days after surgery; the all-cause mortality within 30 days and 1 year after surgery; admission to the intensive care unit (ICU) and length of ICU stay within 30 days after surgery; the length of postoperative hospital stay; and medical costs during hospitalization after surgery. DISCUSSION: The result of this trial (which will be available in September 2019) will confirm whether TEAS before and during anesthesia could alleviate the postoperative pulmonary complications after gastrointestinal surgery in elderly patients, and whether dual-acupoint stimulation is more effective than single-acupoint stimulation. TRIALS REGISTRATIONS: ClinicalTrials.gov, ID: NCT03230045 . Registered on 10 July 2017.

Involvement of PKCα and ERK1/2 signaling pathways in EGCG's protection against stress-induced neural injuries in Wistar rats.

Stress-induced neural injuries are closely linked to the pathogenesis of various neuropsychiatric disorders and psychosomatic diseases. We and others have previously demonstrated certain protective effects of epigallocatechin-3-gallate (EGCG) in stress-induced cerebral impairments, but the underlying protective mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of PKCα and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in EGCG-mediated protection against restraint stress-induced neural injuries in rats. In both open-field and step-through behavioral tests, the restraint stress-induced neuronal impairments were significantly ameliorated by administration of EGCG or green tea polyphenols (GTPs), which was associated with a partial restoration of normal plasma glucocorticoid, dopamine and serotonin levels. Furthermore, the stress-induced decrease of PKCα and ERK1/2 expression and phosphorylation was significantly attenuated by EGCG and to a less extent by GTP administration. Additionally, EGCG supplementation restored the production of adenosine triphosphate (ATP) and the expression of a key regulator of cellular energy metabolism, the peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), in stressed animals. In conclusion, PKCα and ERK1/2 signaling pathways as well as PGC-1α-mediated ATP production might be involved in EGCG-mediated protection against stress-induced neural injuries.

Full-movement neuromuscular electrical stimulation improves plantar flexor spasticity and ankle active dorsiflexion in stroke patients: a randomized controlled study.

OBJECTIVE: To investigate whether full-movement neuromuscular electrical stimulation, which can generate full range of movement, reduces spasticity and/or improves motor function more effectively than control, sensory threshold-neuromuscular electrical stimulation, and motor threshold-neuromuscular electrical stimulation in sub-acute stroke patients. DESIGN: A randomized, single-blind, controlled study. SETTING: Physical therapy room and functional assessment room. PARTICIPANTS: A total of 72 adult patients with sub-acute post-stroke hemiplegia and plantar flexor spasticity. METHOD: Patients received 30-minute sessions of neuromuscular electrical stimulation on the motor points of the extensor hallucis and digitorum longus twice a day, five days per week for four weeks. MEASURES: Composite Spasticity Scale, Ankle Active Dorsiflexion Score, and walking time in the Timed Up and Go Test were assessed at pretreatment, posttreatment, and at two-week follow-up. RESULTS: After four weeks of treatment, when comparing interclass pretreatment and posttreatment, only the full-movement neuromuscular electrical stimulation group had a significant reduction in the Composite Spasticity Scale (mean % reduction = 19.91(4.96)%, F = 3.878, p < 0.05) and improvement in the Ankle Active Dorsiflexion Score (mean scores = 3.29(0.91), F = 3.140, p < 0.05). Furthermore, these improvements were maintained two weeks after the treatment ended. However, there were no significant differences in the walking time after four weeks of treatment among the four groups (F = 1.861, p > 0.05). CONCLUSIONS: Full-movement neuromuscular electrical stimulation with a stimulus intensity capable of generating full movement can significantly reduce plantar flexor spasticity and improve ankle active dorsiflexion, but cannot decrease walking time in the Timed Up and Go Test in sub-acute stroke patients.

Myelinated Afferents Are Involved in Pathology of the Spontaneous Electrical Activity and Mechanical Hyperalgesia of Myofascial Trigger Spots in Rats.

Myofascial trigger points (MTrPs) are common causes for chronic pain. Myelinated afferents were considered to be related with muscular pain, and our clinical researches indicated they might participate in the pathology of MTrPs. Here, we applied myofascial trigger spots (MTrSs, equal to MTrPs in human) of rats to further investigate role of myelinated afferents. Modified pyridine-silver staining revealed more nerve endings at MTrSs than non-MTrSs (P < 0.01), and immunohistochemistry with Neurofilament 200 indicated more myelinated afferents existed in MTrSs (P < 0.01). Spontaneous electrical activity (SEA) recordings at MTrSs showed that specific block of myelinated afferents in sciatic nerve with tetrodotoxin (TTX) led to significantly decreased SEA (P < 0.05). Behavioral assessment showed that mechanical pain thresholds (MPTs) of MTrSs were lower than those of non-MTrSs (P < 0.01). Block of myelinated afferents by intramuscular TTX injection increased MPTs of MTrSs significantly (P < 0.01), while MPTs of non-MTrSs first decreased (P < 0.05) and then increased (P > 0.05). 30 min after the injection, MPTs at MTrSs were significantly lower than those of non-MTrSs (P < 0.01). Therefore, we concluded that proliferated myelinated afferents existed at MTrSs, which were closely related to pathology of SEA and mechanical hyperalgesia of MTrSs.