The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

Unraveling the unique butyrate re-assimilation mechanism of Clostridium sp. strain WK and the application of butanol production from red seaweed Gelidium amansii through a distinct acidolytic pretreatment.

Exploration of the algae-derived biobutanol synthesis has become one of the hotspots due to its highly cost-effective and environment-friendly features. In this study, a solventogenic strain Clostridium sp. strain WK produced 13.96 g/L butanol with a maximal yield of 0.41 g/g from glucose in the presence of 24 g/L butyrate. Transcriptional analysis indicated that the acid re-assimilation of this strain was predominantly regulated by genes buk-ptb rather than ctfAB, explaining its special phenotypes including high butyrate tolerance and the pH-independent fermentation. In addition, a butyric acid-mediated hydrolytic system was established for the first time to release a maximal yield of 0.35 g/g reducing sugars from the red algal biomass (Gelidium amansii). Moreover, 4.48 g/L of butanol was finally achieved with a significant enhancement by 29.9 folds. This work reveals an unconventional metabolic pathway for butanol synthesis in strain WK, and demonstrates the feasibility to develop renewable biofuels from marine resources.

Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity.

The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1-2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6,10-13, 14) and four other compounds (17, 18, 20,28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.

Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects.

OBJECTIVES: Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. KEY FINDINGS: Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. SUMMARY: Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.

The Influence of Standardized Residency Training on Trainees' Willingness to Become a Doctor: A Comparison between Traditional Chinese Medicine and Western Medicine.

A standardized residency training program (SRT) was launched in Shanghai in 2010, for both Western Medicine (WM) and Traditional Chinese Medicine (TCM). This study aimed to assess whether the program impacted trainees' willingness to become a doctor and whether the program had different effects among WM and TCM trainees. A structured questionnaire was distributed to 2114 trainees to assess their perceptions and satisfaction with the program and their willingness to become a doctor after the exposure to the program. The trainees' characteristics were compared between WM and TCM specialties using X2 tests. The potential factors associated with trainees' perception of the program and willingness to become a doctor after the exposure to the SRT program were assessed by multiple linear and logistic regression models. Compared to WM trainees (n = 1853), TCM trainees (n = 261) would be more likely to become doctors if there were no SRT program (p = 0.003). Both individual and program-wide (different specialties) factors contributed to trainees' perception, overall satisfaction, and willingness. Only specialty played an independent role in the associations with all three outcome variables. Inequality of characteristics between TCM and WM trainees reduced TCM trainees' willingness to become a doctor after the exposure to the SRT program.

Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis.

BACKGROUND: Surgical wound infiltration with local anesthetics is common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacaine can provide up to 92 hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults. It is also commonly used by pediatric surgeons, but its safety profile in this age group has not been described. AIMS: The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal bupivacaine compared to plain bupivacaine for surgical wound infiltration. METHODS: We conducted a retrospective, single center, assessor blinded cohort study of pediatric surgical inpatients having open or laparoscopic surgery in the Cleveland Clinic between 2013 and 2017 and receiving wound infiltration with local anesthetics. We compared the incidence of local anesthetic systemic toxicity among those who received any dose of liposomal bupivacaine and those who received plain bupivacaine. Groups were matched 1:2 according to procedure type, age, and physical status score. Local anesthetic systemic toxicity was primarily defined as at least two signs or symptoms possibly related to anesthetic toxicity, as judged by two independent adjudicators blinded to the type of local anesthetic. A sensitivity analysis compared the incidence of a single sign/symptom possibly related to anesthetic toxicity. RESULTS: A total of 924 surgical cases were included in the final analysis (356 liposomal bupivacaine and 568 plain bupivacaine cases). The primary outcome did not occur in any patient. The sensitivity analysis found three cases in the liposomal bupivacaine group and two cases in the plain bupivacaine group having a single sign/symptom possibly related to local anesthetic administration (relative risk 2.4, 95% CI 0.4-14.0, P = 0.38). CONCLUSION: In a cohort of pediatric surgical patients receiving wound infiltration with either plain or liposomal bupivacaine, we identified no cases of local anesthetic systemic toxicity syndrome, and only few patients with any sign or symptom that could potentially be related to local anesthetic toxicity.

ST37 Klebsiella pneumoniae: development of carbapenem resistance in vivo during antimicrobial therapy in neonates.

AIM: To investigate the mechanism leading to in vivo carbapenem resistance development in Klebsiella pneumoniae. METHODS: Carbapenemase was detected using the modified carbapenem inactivation method. ß-lactamases resistant genes were identified by PCR and sequencing. Clonal relatedness was evaluated by random amplified polymorphic DNA and multiple locus sequence typing. The relationship between sequence typing and resistant genes was analyzed by using the chi-squared test. RESULTS: All ST37 carbapenem-resistant isolates were blaOXA-1 positive and all ST37 carbapenem-sensitive isolates were blaOXA-1 negative at Stage I. A significant relationship between carbapenem resistance and blaOXA-1 was observed. The blaOXA-1 -positive rate was significantly higher in ST37 K. pneumoniae than others. CONCLUSION: This is the first study about the development of carbapenem resistance in vivo potentially mediated by blaOXA-1 in ST37 K. pneumoniae among neonates.

Psychometric Evaluation of Chinese-Language 44-Item and 10-Item Big Five Personality Inventories, Including Correlations with Chronotype, Mindfulness and Mind Wandering.

The 44-item and 10-item Big Five Inventory (BFI) personality scales are widely used, but there is a lack of psychometric data for Chinese versions. Eight surveys (total N = 2,496, aged 18-82), assessed a Chinese-language BFI-44 and/or an independently translated Chinese-language BFI-10. Most BFI-44 items loaded strongly or predominantly on the expected dimension, and values of Cronbach's alpha ranged .698-.807. Test-retest coefficients ranged .694-.770 (BFI-44), and .515-.873 (BFI-10). The BFI-44 and BFI-10 showed good convergent and discriminant correlations, and expected associations with gender (females higher for agreeableness and neuroticism), and age (older age associated with more conscientiousness and agreeableness, and also less neuroticism and openness). Additionally, predicted correlations were found with chronotype (morningness positive with conscientiousness), mindfulness (negative with neuroticism, positive with conscientiousness), and mind wandering/daydreaming frequency (negative with conscientiousness, positive with neuroticism). Exploratory analysis found that the Self-discipline facet of conscientiousness positively correlated with morningness and mindfulness, and negatively correlated with mind wandering/daydreaming frequency. Furthermore, Self-discipline was found to be a mediator in the relationships between chronotype and mindfulness, and chronotype and mind wandering/daydreaming frequency. Overall, the results support the utility of the BFI-44 and BFI-10 for Chinese-language big five personality research.

Unconventional pore and defect generation in molybdenum disulfide: application in high-rate lithium-ion batteries and the hydrogen evolution reaction.

A 2H-MoS2 (H=hexagonal) ultrathin nanomesh with high defect generation and large porosity is demonstrated to improving electrochemical performance, including in lithium-ion batteries (LIBs) and the hydrogen evolution reaction (HER), with the aid of a 3D reduced graphene oxide (RGO) scaffold as fast electron and ion channels. The 3D defect-rich MoS2 nanomesh/RGO foam (Dr-MoS2 Nm/RGO) can be easily obtained through a one-pot cobalt acetate/graphene oxide (GO) co-assisted hydrothermal reaction, in which GO, cobalt and acetate ions are co-morphology-controlling agents and defect inducers. As an anode material for LIBs, Dr-MoS2 Nm/RGO has only a 9% capacity decay at a 10 C discharge rate versus 0.2 C with stable cyclability at the optimized composition (5 wt% RGO to MoS2 and 2 mol% Co to Mo), and significantly achieves 810 mA h g(-1) at a high current density of 9.46 A g(-1) over at least 150 cycles. Moreover, Dr-MoS2 Nm/RGO exhibits superior activity for the HER with an overpotential as low as 80 mV and a Tafel slope of about 36 mV per decade. In contrast to the MoS2 nanosheet/RGO (MoS2 Ns/RGO), which is synthesized in the absence of cobalt ions, Dr-MoS2 Nm/RGO provides high interconnectivity for efficient lithium-ion transport, and rich defects as electrochemically active sites. DFT is used to prove the existence of rich defects due to anion replacement to become a Co-Mo-S atomic structure, releasing inert basal planes to active sites.

The effects of visual imagery on face identification: an ERP study.

The present study tested the hypothesis that the effects of mental imagery on subsequent perception occur at a later matching stage in perceptual identification, but not in the early perceptual stage as in perceptual detection. The behavioral results suggested that the effect of visual imagery on visual identification is content-specific, i.e., imagining a congruent face facilitates face identification, whereas a mismatch between imagery and perception leads to an interference effect. More importantly, the ERP results revealed that a more negative N2 response to the subsequent visual face stimuli was elicited over fronto-central sites in the mismatch and no-imagery conditions as compared to that in the match condition, with the early P1 and N170 components independent of manipulations. The latency and distribution of the neural effects demonstrate that the matching step, but not the earlier perceptual process, is affected by the preceding visual imagery in the context of face identification. We discuss these results in a broader context that the imagery-perception interaction may depend on task demand.

Enhanced mismatch negativity in adolescents with posttraumatic stress disorder (PTSD).

The mismatch negativity (MMN) is observed following rare or unique sensory events, and reflects pre-attentional sensory processing of unexpected stimuli. The MMN is altered in several mental illnesses, including post-traumatic stress disorder (PTSD), but did not yield consistent results. We measured MMN in 27 survivors of the Wenchuan earthquake, including 13 who were diagnosed with PTSD, to determine if pre-attentive processing in the auditory cortex was altered by this disease. The amplitude of MMN was significantly greater in the PTSD group compared to the control group. In contrast, no significant group difference was found in the N1 potential, an event-related potential that reflects cortical transmission of sensory information. These results demonstrated an increased sensitivity to deviant stimuli in PTSD that may reflect a chronic state of hyperarousal and hypervigilance in trauma victims.

Cisplatin-induced gastric dysrhythmia and emesis in dogs and possible role of gastric electrical stimulation.

The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation.