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Introduction: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML)., Methods: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection., Results: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress., Conclusion: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future., (© 2024 John Wiley & Sons Ltd.)

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L . exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aβ). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented β-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated β-amyloid (Aβ1-42)-peptides. Excess deposition of amyloid-β oligomers (AβO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L . (TFDM) inhibited Aβ1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aβ1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 μM Aβ1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aβ1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.

Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD)., Objectives: The authors assessed differences in Lp(a) testing and levels by disaggregated race, ethnicity, and ASCVD risk., Methods: This was a retrospective cohort study of patients from a large California health care system from 2010 to 2021. Eligible individuals were ≥18 years old, with ≥2 primary care visits, and complete race and ethnicity data who underwent Lp(a) testing. Race and ethnicity were self-reported and categorized as follows: non-Hispanic (NH) White, NH-Black, Hispanic (Mexican, Puerto Rican, other), NH-Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other). Logistic regression models tested associations between elevated Lp(a) (≥50 mg/dL) and race, ethnicity, and ASCVD risk., Results: 13,689 (0.9%) individuals underwent Lp(a) testing with a mean age of 54.6 ± 13.8 years, 49% female, 28.8% NH Asian. Over one-third of those tested had Lp(a) levels ≥50 mg/dL, ranging from 30.7% of Mexican patients to 62.6% of NH-Black patients. The ASCVD risk of those tested varied by race: 73.6% of Asian Indian individuals had <5% 10-year risk, whereas 27.2% of NH-Black had established ASCVD. Lp(a) prevalence ≥50 mg/dL increased across the ASCVD risk spectrum. After adjustment, Hispanic (OR: 0.76 [95% CI: 0.66-0.88]) and Asian (OR: 0.88 [95% CI: 0.81-0.96]) had lower odds of Lp(a) ≥50 mg/dL, whereas Black individuals had higher odds (OR: 2.46 [95% CI: 1.97-3.07])., Conclusions: Lp(a) testing is performed infrequently. Of those tested, Lp(a) levels were frequently elevated and differed significantly across disaggregated race and ethnicity groups. The prevalence of elevated Lp(a) increased with increasing ASCVD risk, with significant variation by race and ethnicity., Competing Interests: Dr Rodriguez has received grants from the 10.13039/100000002National Institutes of Health/10.13039/100000050National Heart, Lung, and Blood Institute (1K01HL144607; R01HL168188), the American Heart Association/Harold Amos Faculty Development Program, and the 10.13039/100000862Doris Duke Charitable Foundation (#2022051) during the conduct of the study. Dr Palaniappan has received grants from the 10.13039/100000002National Institutes of Health/10.13039/100000050National Heart, Lung, and Blood Institute (K24 HL150476). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Rodriguez has consulting relationships with Healthpals, Novartis, NovoNordisk (CEC), Esperion Therapeutics, Movano Health, Kento Health, Inclusive Health, Edwards, and Arrowhead Pharmaceuticals outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Excess opioid prescribing after surgery can lead to prolonged opioid use and diversion. We interviewed surgeons who were part of a three-group cluster-randomised controlled trial aimed at reducing prescribed opioid quantities after surgery via two versions of a monthly emailed behavioural 'nudge' (messages encouraging but not mandating compliance with social norms and clinical guidelines around prescribing) at the end of the implementation year in order to understand surgeons' reasoning for changing or continuing their prescribing behaviour as a result of the intervention and the context for their rationale., Methods: The study took place at a large healthcare system in northern California with surgeons from three surgical specialties-orthopaedics, obstetrics/gynaecology and general surgery. Following the intervention period, we conducted semistructured interviews with 36 surgeons who had participated in the trial, ensuring representation across trial arm, specialty and changes in prescribing quantities over the year. Interviews focused on reactions to the nudges, impacts of the nudges on prescribing behaviours and other factors impacting prescribing. Three study team members coded and analysed the transcribed interviews., Results: Nudges were equally effective in reducing postsurgical opioid prescribing across surgical specialties and between intervention arms. Surgeons were generally receptive to the nudge intervention, noting that it reduced the size of their discharge opioid prescriptions by improving their awareness and intentionality around prescribing. Most were unaware that clinical guidelines around opioid prescribing existed. Some had reservations regarding the accuracy and context of information provided in the nudges, the prescription quantities encouraged by the nudges and feelings of being watched or admonished. A few described discussing the nudges with colleagues. Respondents emphasised that the prescribing behaviours are informed by individual clinical experience and patient-related and procedure-related factors., Conclusions: Surgeons were open to learning about their prescribing behaviour through comparisons to guidelines or peer behaviour and incorporating this feedback as one of several factors that guide discharge opioid prescribing. Increasing awareness of clinical guidelines around opioid prescribing is important for curbing postsurgical opioid overprescribing., Trial Registration Number: NCT05070338., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Racial and ethnic minorities receive opioid prescriptions at lower rates and dosages than White patients. Though opioid stewardship interventions can improve or exacerbate these disparities, there is little evidence about these effects. We conducted a secondary analysis of a cluster-randomized controlled trial conducted among 438 clinicians from 21 emergency departments and 27 urgent care clinics. Our objective was to determine whether randomly allocated opioid stewardship clinician feedback interventions that were designed to reduce opioid prescriptions had unintended effects on disparities in prescribing by patient race and ethnicity., Methods: The primary outcome was likelihood of receiving a low-pill prescription (low ≤10 pills, medium 11-19 pills, high ≥20 pills). Generalized mixed-effects models were used to determine patient characteristics associated with low-pill prescriptions during the baseline period. These models were then used to determine whether receipt of a low-pill prescription varied by patient race or ethnicity during the intervention period between usual care and three opioid stewardship interventions: (1) individual audit feedback, (2) peer comparison feedback, and (3) combined (individual audit + peer comparison) feedback., Results: Compared with White patients, Black patients were more likely to receive a low-pill prescription during the baseline (adjusted odds ratio [OR] 1.18, 95% confidence interval [CI] 1.06-1.31, p = 0.002) and intervention (adjusted OR 1.43, 95% CI 1.07-1.91, p = 0.015). While combined feedback was associated with an overall increase in low-pill prescriptions as intended (adjusted OR 1.89, 95% CI 1.28-2.78, p = 0.001), there were no significant differences in treatment effects of any of the interventions by patient race and ethnicity., Conclusions: Combined individual audit and peer comparison feedback was associated with fewer opioid pills per prescription equally by patient race and ethnicity. However, the intervention did not significantly close the baseline disparity in prescribing by race., (© 2023 Society for Academic Emergency Medicine.)

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Wu, He, Wang, Zhao, Huang, Yan and Jiang.)

Peer comparison feedback is a promising strategy for reducing opioid prescribing and opioid-related harms. Such comparisons may be particularly impactful among underestimating clinicians who do not perceive themselves as high prescribers relative to their peers. But peer comparisons could also unintentionally increase prescribing among overestimating clinicians who do not perceive themselves as lower prescribers than peers. The objective of this study was to assess if the impact of peer comparisons varied by clinicians' preexisting opioid prescribing self-perceptions. Subgroup analysis of a randomized trial of peer comparison interventions among emergency department and urgent care clinicians was used. Generalized mixed-effects models were used to assess whether the impact of peer comparisons, alone or combined with individual feedback, varied by underestimating or overestimating prescriber status. Underestimating and overestimating prescribers were defined as those who self-reported relative prescribing amounts that were lower and higher, respectively, than actual relative baseline amounts. The primary outcome was pills per opioid prescription. Among 438 clinicians, 54% (n = 236) provided baseline prescribing self-perceptions and were included in this analysis. Overall, 17% (n = 40) were underestimating prescribers whereas 5% (n = 11) were overestimating prescribers. Underestimating prescribers exhibited a differentially greater decrease in pills per prescription compared to nonunderestimating clinicians when receiving peer comparison feedback (1.7 pills, 95% CI, -3.2 to -0.2 pills) or combined peer and individual feedback (2.8 pills, 95% CI, -4.8 to -0.8 pills). In contrast, there were no differential changes in pills per prescription for overestimating versus nonoverestimating prescribers after receiving peer comparison (1.5 pills, 95% CI, -0.9 to 3.9 pills) or combined peer and individual feedback (3.0 pills, 95% CI, -0.3 to 6.2 pills). Peer comparisons were more impactful among clinicians who underestimated their prescribing compared to peers. By correcting inaccurate self-perceptions, peer comparison feedback can be an effective strategy for influencing opioid prescribing., (Copyright © 2023 the American College of Medical Quality.)

Opioid misuse represents a major public health issue in the United States. One driver is overprescription for acute pain, with the size of initial prescription associated with subsequent long-term use. However, little work has been done to elicit clinician feedback about interventions to reduce opioid prescribing. To address this knowledge gap, qualitative analyses were conducted with clinicians who participated in a randomized controlled trial in which clinicians received monthly emailed feedback notifications about their opioid prescribing behaviors. Semistructured telephone interviews were conducted (N = 12) with urgent care (N = 7) and emergency department (N = 5) clinicians who participated in the trial between November 2020 and April 2021. Clinicians appreciated feedback about their prescribing behavior and found comparative data with peer clinicians to be most useful. Sharing opioid prescribing feedback data with clinicians can be an acceptable way to address opioid prescribing among emergency and urgent care clinicians., (Copyright © 2023 the American College of Medical Quality.)

Chinese medicine (CM) has thousands of years of experience in prevention of diseases. As for CM, people's constitution is closely related to their health status, thus recognition of CM constitution is the fundamental and core content of research on constitution types. With development of technologies such as sensors, artificial intelligence and big data, objectification of the four diagnostic methods of CM has gradually matured, bringing changes in the mindset and innovations in technical means for recognition of CM constitution. This paper presents a systematic review of the latest research trends in constitution recognition based on objectification of diagnostic methods in CM., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Oreocharispolyneura , a new species from southern Yunnan, China, is described and illustrated. It is morphologically similar to O.rhytidophylla by having more obvious lateral veins forming a crosslinked network on the adaxial surface of leaf blades, but can be distinguished by having more lateral veins (12-15 pairs vs. 7-9 pairs) of leaf blades, shorter corolla tubes (the length ratio of corolla tube to corolla lobes = 1.2-2.9 vs. 3.4-6) and shorter pistils (6-8 mm long vs. 27-30 mm long). In addition, a detailed morphological description, a photographic illustration, the distribution and phenology of the new species are presented., (Yan-Xiong Gong, Hong-Bo Ding, Xiang-Shuai Yan, Fang Wen, Yao-Hua Tian, Yun-Hong Tan.)

Fast charging promotes Li dendrite formation and its growth on graphite anodes, which affects cell performance in Li-ion batteries (LIBs). This work reports the formation of a robust SEI layer by introducing a KPF 6 inorganic additive into the electrolyte. An optimal concentration of 0.001 M KPF 6 effectively inhibits the growth of Li dendrites at 2C charging rates, compared with a commercial electrolyte. Electrolytes containing a KPF 6 additive are shown here to deliver dual effects to mitigate the growth of dendrites. A thin LiF-rich SEI layer is formed on graphite, which blocks the electron leakage pathways. Additionally, K + resides at defect sites (such as particle boundaries) due to its faster diffusion rate and blocks the incoming Li + and restricts the growth of Li dendrites. The electrolyte with optimum concentration of KPF 6 , i.e., 0.001 M, effectively directs Li + transport through the thin, durable, and low resistance LiF-rich SEI layer. This has implications for fast charging through optimization of the electrode/electrolyte interphase by controlling additive concentrations.

Introduction: Surgical patients are commonly prescribed more opioids at discharge than needed to manage their postoperative pain. These excess opioids increase the risks of new persistent opioid use, opioid-induced ventilatory impairment and opioid diversion. This study tests the effectiveness of two behavioural nudges, one based on peer behaviour and one based on best practice guidelines, in reducing excessive postoperative opioid prescriptions., Methods and Analysis: The study will be conducted at 19 hospitals within a large healthcare delivery system in northern California, USA. Three surgical specialties (general surgery, orthopaedic surgery and obstetric/gynaecological surgery) at each hospital will be randomised either to a control group or to one of two active intervention arms. One intervention is grounded in the theory of injunctive norms, and provides feedback to surgeons on their postoperative opioid prescribing relative to prescribing guidelines endorsed by their institution. The other intervention draws from the theory of descriptive norms, and provides feedback similar to the first intervention but using peers' behaviour rather than guidelines as the benchmark for the surgeon's prescribing behaviour. The interventions will be delivered by a monthly email. Both interventions will be active for twelve months. The effects of each intervention relative to the control group and to each other will be tested using a four-level hierarchical model adjusted for multiple hypothesis testing., Ethics and Dissemination: Using behavioural nudges rather than rigid policy changes allows us to target excessive prescribing without preventing clinicians from using their clinical judgement to address patient pain. All study activities have been approved by the RAND Human Subjects Protection Committee (ID 2018-0988). Findings will be disseminated through conference presentations, peer-reviewed publications and social media accounts., Trial Registration Number: NCT05070338., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To study the value of molecular classification in postoperative adjuvant therapy for endometrial carcinoma (EC). Methods: Patients with stage Ⅰ EC who underwent surgical-pathological staging surgery and molecular classification in Peking University Third Hospital from January 2020 to April 2022 were retrospectively analyzed. The influence of different molecular types of EC on postoperative adjuvant therapy were studied. Results: The age of the 196 patients was (55.1±10.2) years old, and the body mess index (BMI) was (26.0±3.9) kg/m 2 . Molecular classification was performed in 196 stage ⅠEC patients, identifying the 4 subgroups: POLE mutation (POLEmut, n =19, 9.7%), mismatch repair-deficient (dMMR, n =28, 14.3%), no-specific molecular profile (NSMP, n =142, 72.4%) and p53 mutation (p53abn, n =7, 3.6%). Molecular classification was one of the influencing factors on the selection of postoperative adjuvant therapy for EC patients ( P =0.003). POLEmut, dMMR and NSMP subtypes were not the variables in selecting radiotherapy or combined chemo-radiotherapy postoperatively. p53abn subtype was not the influencer for radiotherapy, however, it may contribute to the selection of combined chemo-radiotherapy postoperatively ( P <0.001). Conclusion: The p53abn subtype in the molecular classification is an influencing factor in the selection of combined chemo-radiotherapy for EC patients postoperatively.

An initial opioid prescription with a greater number of pills is associated with a greater risk for future long-term opioid use, yet few interventions have reliably influenced individual clinicians' prescribing. Our objective was to evaluate the effect of feedback interventions for clinicians in reducing opioid prescribing. The interventions included feedback on a clinician's outlier prescribing (individual audit feedback), peer comparison, and both interventions combined. We conducted a four-arm factorial pragmatic cluster randomized trial at forty-eight emergency department (ED) and urgent care (UC) sites in the western US, including 263 ED and 175 UC clinicians with 294,962 patient encounters. Relative to usual care, there was a significant decrease in pills per prescription both for peer comparison feedback (-0.8) and for the combination of peer comparison and individual audit feedback (-1.2). This decrease was sustained during follow-up. There were no significant changes for individual audit feedback alone, and no interventions changed the proportion of encounters with an opioid prescription.

Laboratory data from Electronic Health Records (EHR) are often used in prediction models where estimation bias and model performance from missingness can be mitigated using imputation methods. We demonstrate the utility of imputation in two real-world EHR-derived cohorts of ischemic stroke from Geisinger and of heart failure from Sutter Health to: (1) characterize the patterns of missingness in laboratory variables; (2) simulate two missing mechanisms, arbitrary and monotone; (3) compare cross-sectional and multi-level multivariate missing imputation algorithms applied to laboratory data; (4) assess whether incorporation of latent information, derived from comorbidity data, can improve the performance of the algorithms. The latter was based on a case study of hemoglobin A1c under a univariate missing imputation framework. Overall, the pattern of missingness in EHR laboratory variables was not at random and was highly associated with patients' comorbidity data; and the multi-level imputation algorithm showed smaller imputation error than the cross-sectional method., (© 2021. The Author(s).)

The development of endoscopic treatment technology has further promoted the minimally invasive treatment of early gastric cancer (EGC). Endoscopic treatment has achieved better therapeutic effects in terms of safety and prognosis and is the preferred treatment method for patients who meet the indications for endoscopic treatment. However, the consequent problem is that some patients receiving endoscopic treatment may undergo non-curative resection, and the principle of follow-up management for non-curative resection patients deserves further attention. In addition, there are still debates on how to improve the accuracy of clinical staging, select a reasonable treatment method for patients who meet the expanded indications for endoscopic treatment, manage patients with positive endoscopic surgical margins, conduct research on function-preserving surgery, and manage the treatment of EGC under the current situation in China. Consequently, we aim to review current indications for endoscopic submucosal dissection of EGC in order to better inform treatment options., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To summarize the clinical and Laboratory characteristics of patients with multiple myeloma (MM) and analyze the prognostic factors., Methods: Two hundred MM patients were retrospectively analyzed for the following parameters, including peripheral blood, bone marrow morphology, cytogenetics, clinical staging, and response to the chemotherapy in order to summarize related factors affecting overall survival (OS). The prognostic factors were also analyzed., Results: 200 patients with MM were divided into 3 groups according to bone marrow plasma cell percentage (BMPC%) in bone marrow smears: ＜10% group (74 cases, 37.0%), 10%-50% group (75 cases, 37.5%), ＞50% group (51 cases, 25.5%). Compared with the other two groups, patients in BMPC%<10% group were characterized by lower clinical staging levels, lower rates of 13q14 deletion and t(11;14) positive, better response to chemotherapy and favorable three-year OS rate. The univariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%＜10%, WBC＜7.5×10 9 /L, Hb≥68 g/L, PLT≥150×10 9 /L, β 2 -MG＜5.5 mg/L, LDH≤230 U/L, Durie-Salmon staging A, achievement of VGPR or better outcome after the first chemotherapy, achievement VGPR or better outcome after the fourth chemotherapy, and presence of autologous hematopoietic stem cell transplantation(auto-HSCT)(P<0.05). The multivariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%≤50%, WBC＜7.5×10 9 /L, Hb≥68 g/L, achievement of VGPR or better outcome after the fourth chemotherapy (P<0.05)., Conclusion: The clinical characteristics are different among MM patients with different BMPC% in bone marrow smears at initial diagnosis, and prognostic analysis shows that the BMPC% in bone marrow smears has an effect on OS rate. BMPC% in bone marrow smears at initial diagnosis, age, WBC, Hb, response to the fourth chemotherapy are also the main factors impacting the prognosis of patients.

We propose to create nanospheres in aqueous solutions from coordination polymers of Ag+ with a combination of a hydrophilic and a hydrophobic thiol, of diameter ca. 2.7 nm in the case of using cysteine and n-butanethiol. A spectral probe for the formation of the nanospheres is a reversal of the CD signal at 253 nm from negative in the case of cysteine alone to positive when cysteine and n-BuSH are both employed, together with an amplification.

We report a new scheme for chiral recognition using coordination polymers of Ag + with a chiral thiol ligand that contains a binding group. N -Benzoyl-l-cysteine ethyl ester equipped with a boronic acid group at the para position of the phenyl ring forms coordination polymers with Ag + in alkaline aqueous solutions that exhibit excellent selectivity toward a d-glucose enantiomer over l-glucose, while the coordination polymers from the d-cysteine-based thiol ligand are specific for l-glucose. It is assumed that a conformation change occurs upon interaction of a saccharide molecule with the polymeric chain receptor, for which the next binding is promoted, leading to the highly effective chiral recognition, despite the flexible nature of the polymeric receptor.

Background: Inflammatory bowel disease (IBD) associates with damage to the enteric nervous system (ENS), leading to gastrointestinal (GI) dysfunction. Oxidative stress is important for the pathophysiology of inflammation-induced enteric neuropathy and GI dysfunction. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a dual functioning protein that is an essential regulator of the cellular response to oxidative stress. In this study, we aimed to determine whether an APE1/Ref-1 redox domain inhibitor, APX3330, alleviates inflammation-induced oxidative stress that leads to enteric neuropathy in the Winnie murine model of spontaneous chronic colitis., Methods: Winnie mice received APX3330 or vehicle via intraperitoneal injections over 2 weeks and were compared with C57BL/6 controls. In vivo disease activity and GI transit were evaluated. Ex vivo experiments were performed to assess functional parameters of colonic motility, immune cell infiltration, and changes to the ENS., Results: Targeting APE1/Ref-1 redox activity with APX3330 improved disease severity, reduced immune cell infiltration, restored GI function ,and provided neuroprotective effects to the enteric nervous system. Inhibition of APE1/Ref-1 redox signaling leading to reduced mitochondrial superoxide production, oxidative DNA damage, and translocation of high mobility group box 1 protein (HMGB1) was involved in neuroprotective effects of APX3330 in enteric neurons., Conclusions: This study is the first to investigate inhibition of APE1/Ref-1's redox activity via APX3330 in an animal model of chronic intestinal inflammation. Inhibition of the redox function of APE1/Ref-1 is a novel strategy that might lead to a possible application of APX3330 for the treatment of IBD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We propose using the formation of coordination polymers of Ag+ to probe differences between the perfluorinated alkyl chain and the alkyl chain by deriving a thiol ligand, N-(perfluoroalkanoyl)cysteine. Rapid formation in EtOH of P-/M-helical nanofibrils of high thermostability was found for N-(perfluorooctanoyl)-l-/d-cysteine ethyl esters at the μM level upon mixing with Ag+, but not for the octanoyl counterpart. This difference was also observed in terms of circular dichroism-enantiomeric excess dependence.

Proline based receptors (1-14) attached with phenylboronic acid and benzaldehyde binding groups at the N-/C- or C-/N-termini of the proline residue were created for chiral recognition of l-/d-DOPA, in an attempt to examine if balancing the two binding events would influence the recognition. By changing the positions of boronic acid and aldehyde groups substituted on the phenyl rings (1-4, 5-8) and the site at which phenylboronic acid and benzaldehyde moieties attached respectively to the N- and C-termini or C- and N-termini of the proline residue (1-4vs.5-8), and by introducing an electron-withdrawing fluorine atom in the phenyl ring of the weaker binder the benzaldehyde moiety (11vs.1, 14vs.5), we were able to show that a better balance of the two binding events does improve the chiral recognition. This finding can only be made with the current version of receptors that were equipped with two different binding groups. Together with the finding that the chiral recognition performance in mixed organic-aqueous solutions is tunable by varying the solvent composition, we have now arrived at a protocol for designing proline based receptors for extended applications in chiral recognition.

Objective: To study the high risk factors for the transformation into acute myeloid leukemia(AML) in patients with intermediate and high risk myelodysplastic syndrome(MDS) treated by decitabine-based regimen., Methods: The clinical characterstics of 60 intermediate and high risk MDS patients and the factors of its transformed into AML were retrospectively analyzed., Results: The overall response rate(ORR) of the patients suffered from intermediate and high risk MDS treated by decitabine-based regimen was 65.0％(39/60), among the 60 cases 17 achieved complete remission(CR), 5 achieved morrow complete remission(mCR), 4 achieved partial remission(PR) and 13 achieved hematologic improvement(HI). Twenty-one cases(35.0%) were transformed into AML among 60 cases of intermediate and high risk MDS treated by decitabine-based regimen. The median time of transformation from intermediate and high risk MDS into AML was 10.0 months(1.6-32.0). χ 2 or Fisher's exact test showed that 2016 WHO MDS diagnostic subgrouping, myeloid hyperplasia markedly active, delayed interval of decitabine-based treatment associated with the transformation from intermediate to high risk MDS into AML (χ 2 =9.878，P=0.031；χ 2 =4.319，P=0.038；χ 2 =6406，P=0.011); Univariate analysis of Kaplan-Meier test showed that 2016 WHO MDS diagnostic subgroups, bone marrow blast cell ratio, bone marrow dysplasia coefficients, prolonged interval of decitabine-based treatment associated with the transformation from intermediate and high risk MDS into AML (P=0.015，P=0.008，P=0.012，P=0.032); multivariate analysis showed the bone marrow blast cell ratio and the bone marrow dysplasia coefficients were independent risk factors for the transformation from intermediate to high risk MDS into AML (P=0.022，P=0.018)., Conclusion: The bone marrow blast cell ratio and the bone marrow dysplasia coefficients are independent risk factors of transformation into AML in the patients with intermediate and high risk MDS treated by decitabine-based regimen. The regular interval of dicitabine treatment is beneficial to maintain the stability of patients conditions.

We report coordination polymers forming from Ag + and a chiral thiol ligand that bears a β-turn structure, exhibiting supramolecular chirality showing both the majority rules effect (MRE) and the racemate rules effect (RRE).

IN BRIEF Chronic conditions such as diabetes are largely managed by primary care providers (PCPs), with significant patient self-management. This article describes the development, pilot testing, and fine-tuning of a Web-based digital health solution to help PCPs manage patients with cardiometabolic diseases during routine office encounters. It shows that such products can be successfully integrated into primary care settings when they address important unmet needs and are developed with input from end-users., (© 2019 by the American Diabetes Association.)

Objective: To summarize the clinical characteristics of patients with acute myeloid leukemia-type M 2 (AML-M 2 ) and analyze the factors affecting the prognosis., Methods: One hundred eighty-eight AML-M 2 patients were retrospectively analyzed for the following parameters including peripheral blood, immune phenotypes, fusion genes and cytogenetics to explore their significance for the overall survival (OS) and progression-free survival (PFS). The prognostic factors were also analyzed., Results: Among 188 patients with AML-M 2 , the chromosomal abnormality with t (8;21), normal chromosome and other abnormalities accounted for 37% (70/188), 41% (77/188) and 22% (41/188), respectively. For the immunopheno typing of M 2 patients, the hematopoietic progenitor cell differentiation antigen CD117 (96.1%) were mainly expressed, CD34 (81.6%) and HLA-DR (55.9%), and myeloid-associated antigen of CD13 (90.5%) and CD33 (89.4%) were also highly expressed. There were lymphoid-associated antigens expressed in some patients, among which the positive expression rate of CD19 was highest (29.6%), and the next was CD7 (28.5%). The most common accompanied mutations was FLT3 mutation (30.2%). The univariate analysis showed that the patients at age＜50 years old, without extramedullary infiltration, with positive expression of CD19, NPM-1 (-), CEBPA double mutation(+), and HSCT were significant superior in OS and PFS (P＜0.05); the multivariate analysis showed that the patient at age＜50 years old, without extramedullary infiltration, with positive expression of CD19 and CEBPA double mutation (+) were significant superior in OS and PFS (P＜0.05). The analysis indicated that the Karytypes affected only OS (P＜0.05), while the NPM-1 gene mutation positive affected only PFS (P＜0.05). The univarate analysis of factors affecting the survival in 70 AML-M 2 patients with t (8;21) abnormatity showed that the C-KIT gene mutation was a poor factor for OS and PFS., Conclusion: The clinical characteristics are different between M 2 patients with different karyotype, and prognostic analysis shows that the karytypes have an impact on overall survival; age, extramedullary infiltration, CD19 expression and CEBPA double mutation are also the main factors impacting the prognosis of patients.

Public water supply facilities are vulnerable to intentional intrusion. In particular, Water Distribution Network (WDN) has become one of the most important public facilities that are prone to be attacked because of its wide coverage and constant open operation. In recent years, water contamination incidents happen frequently, causing serious losses and impacts to the society. Various measures have been taken to tackle this issue. Pollution or contamination isolation by localizing the contamination via sensors and scheduling certain valves have been regarded as one of the most promising solutions. The main challenge is how to schedule water valves to effectively isolate contamination and reduce the residual concentration of contaminants in WDN. In this paper, we are motivated to propose a reinforcement learning based method for valve real time scheduling by treating the sensing data from the sensors as state, and the valve scheduling as action, thus we can learn scheduling policy from uncertain contamination events without precise characterization of contamination source. Simulation results show that our proposed algorithm can effectively isolate the contamination and reduce the risk exclosure to the customers.

Objective: The aim of this study was to research, develop and assess the feasibility of using basic statistical parameters derived from renogram, "mean count value (MeanCV) and "median count value (MedianCV)", as novel indices in the diagnosis of renal obstruction through diuresis renography., Subjects and Methods: First, we re-digitalized and normalized 132 renograms from 74 patients in order to derive the MeanCV and MedianCV. To improve the performance of the parameters, we extrapolated renograms by a two-compartmental modeling. After that, the cutoff points for diagnosis using each modified parameter were set and the sensitivity and specificity were calculated in order to determine the best variants of MeanCV and MedianCV that could differentiate renal obstruction status into 3 distinct classes - i) unobstructed, ii) slightly obstructed, and iii) heavily obstructed., Results: The modified MeanCV and MedianCV derived from extended renograms predicted the severity of the renal obstruction. The most appropriate variants of MeanCV and MedianCV were found to be the MeanCV 50 and the MedianCV 60 . The cutoff points of MeanCV 50 in separating unobstructed and obstructed classes as well as slightly and heavily obstructed classes were 0.50 and 0.72, respectively. The cutoff points of MedianCV 60 in separating unobstructed and obstructed classes as well as slightly and heavily obstructed classes were 0.35 and 0.69, respectively. Notably, MeanCV 50 and MedianCV 60 were not significantly influenced by either age or gender., Conclusions: The MeanCV 50 and the MedianCV 60 derived from a renogram could be incorporated with other quantifiable parameters to form a system that could provide a highly accurate diagnosis of renal obstructions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1-42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity., Competing Interests: None

An extract of Dracocephalum moldevica (DML) was found to exert protective effects on cerebral ischemia-reperfusion injury (CIRI); however, the mechanisms underlying the observed actions of this plant-derived mixture remain to be determined. Thus, the aim of this study was to examine the influence of DML on CIRI rat model induced by middle cerebral artery occlusion (MCAO). The following parameters were measured: (1) viable neurons in the infarcted area using Nissl staining; and (2) immunohistochemistry and Western blot were employed to determine protein expression levels of p53, bcl-2 associated X protein (bax) and B-cell lymphoma-2 (bcl-2), three biomarkers of apoptosis. MCAO significantly decreased the number of viable cortical pyramidal neurons in the infarcted area, while treatment with DML extract significantly elevated the number of viable neurons. MCAO was found to significantly elevate in gene expression levels of p53 and protein expression levels bax accompanied by diminished protein expression levels of bcl-2. Prior administration of DML extract produced marked reduction in gene expression levels of p53 and protein expression levels bax but increased in protein expression levels of bcl-2. Data suggested apoptosis was initiated in MCAO and that DML was effective in treating CIRI via an anti-apoptotic action as evidenced by inhibition of gene expression levels of p53 and protein expression levels of bax with concomitant elevation in protein expression levels of bcl-2. Our findings suggest that extract of DML may prove beneficial in treatment of cerebrovascular disorders.

Ginsenoside Rg1 (GsRg1), derived from the herb Ginseng, was found to exert protective effects in nerve injury; however, the mechanisms underlying these effects remain to be determined. Oxidant stress and apoptosis are known to be involved in sciatic nerve injury. Thus, the aim of this study was to examine whether GsRg1 was able to modify sciatic nerve injury in a rat model. The following parameters were measured: (1) number of spinal cord motoneurons by Nissl staining, (2) oxidation parameters including spinal cord malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as (3) involvement of apoptosis by determining caspase-3 and X-linked inhibitor of apoptosis protein (XIAP) by immunohistochemistry and Western blot. The number of spinal cord motoneurons was significantly reduced after sciatic nerve injury, while treatment with GsRg1 markedly elevated cell number. Sciatic nerve injury markedly increased spinal cord MDA content concomitant with reduced activities of SOD and GSH-Px. GsRg1 significantly decreased MDA content accompanied by elevated activities of SOD and GSH-Px. Further nerve injury significantly diminished protein expression levels of XIAP accompanied by elevated protein expression levels of caspase-3 in the spinal cord. GsRg1 markedly increased protein expression levels of XIAP, but significantly reduced protein expression levels of caspase-3. Data suggest that the protective effects of GsRg1 in sciatic nerve injury may be associated with reduced oxidative stress involving anti-apoptotic pathways.

Cerebral infarction occurs as a consequence of cerebral ischemia-reperfusion injury (CIRI). Ginkgo biloba leaf extract (GbE) is composed predominantly of active ingredients such as flavonoids and terpene lactones and often used to treat cerebrovascular diseases. However, the mechanisms underlying the use of this herbal extract to treat cerebrovascular-mediated damage are not known. The aim of this study was to examine the effectiveness of administration GbE to ameliorate the observed consequences of CIRI. The following parameters were measured: (1) behavioral score (2) infarct area (3) the content of serum malondialdehyde (MDA) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and (4) interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression levels in the infarcted brain tissue. Data demonstrated that treatment with GbE to CIRI rats resulted in significant reduction in cerebral-infarcted area associated with improvement in behavioral score. GbE was found to decrease serum MDA levels concomitant with elevated activity levels of SOD and GSH-PX. Immunohistochemistry and Western blot analysis showed that GbE significantly lowered the levels of IL-6 and TNF-α in the infarcted brain tissue. Data suggest that GbE may be therapeutically effective in improving behavioral score in CIRI rats through reduction of oxidative stress and anti-inflammation in the cerebral infarction region.

Chiral recognition remains a major challenge in the area of molecular receptor design. With this research, we set out to explore the use of proline-based receptors for chiral recognition. Importantly, the proline structure allows for the introduction of at least two different binding groups due to the availability of both an amine and carboxylic acid group. Here we report a proof-of-concept exploration into the chiral recognition of d/l-glucose as a model chiral species, which prefers to bind to at least two boronic acid groups. We evaluated several proline-based receptors incorporating two phenylboronic acid groups, respectively, at the N- and C-termini of the amino acid residue, via amide bonds. We confirmed that the receptors exhibited chiral recognition using CD, 1 H NMR, and 19 F NMR spectroscopy. Given the derivation diversity available, our strategy to use proline-based receptors for chiral recognition holds significant promise for extension to other chiral systems.

Building folded short peptides that are driven by the intramolecular hydrogen bonding in aqueous solutions remains challenging because of their highly competitive intermolecular hydrogen-bonding interactions with water solvent molecules that would have favored the extended conformations. Here, we show folded β-turn structures in acyl amino acid-based N -amidothioureas, the nonclassic azapeptides, in aqueous solutions, as well as in solid-state and organic solvents, by X-ray crystal structures, DFT calculations, 1D and 2D NMR spectra, and absorption and CD spectra. The achiral phenylthiourea chromophore acts as a CD reporter for the β-turn structure that communicates the chirality of the amino acid residue to the achiral thiourea moiety and the relative intensity of the intramolecular hydrogen bond that stabilizes the turn structure. The amidothiourea moiety represents a versatile structural framework for folded short peptides in aqueous environments., Competing Interests: The authors declare no competing financial interest.

Previously, total flavones of Dracocephalum (TFD), derived from Dracocephalum, were found to exert protective effects in cerebral ischemia reperfusion injury (CIRI) in middle cerebral artery occlusion (MCAO) rat model. However, the mechanisms underlying these observed effects of TFD on MCAO-induced rats still remain to be determined. Therefore, the aim of this study was to examine whether TFD alleviated MCAO through mechanisms involving anti-inflammatory and anti-apoptotic using MCAO rats. The following parameters were measured: (1) percentage (%) area of brain infarction; (2) serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and (3) expression protein levels of caspase-3 and AMP-activated protein kinase (AMPK). Results showed that MCAO significantly increased the % area of brain infarction, while TFD administration in these animals markedly reduced % area of brain infarction. A significant elevation on serum levels of TNF-α and IL-6 was noted with MCAO which was markedly reduced by TFD. In addition, MCAO produced a significant rise in protein expression levels of caspase-3 and AMPK. In contrast, TFD markedly lowered protein expression levels of caspase-3 and AMPK. Data suggest that the protective effects of TFD in MCAO model animals may involve inhibition of inflammatory mediator release associated with apoptosis through down regulation of AMPK signaling pathway.

Phenylethanoid glycosides (PHG), derived from Herba cistanche, were found to exert protective effects on cognitive dysfunctions by improving synaptic plasticity in Alzheimer's disease (AD) rat model. However, the mechanisms underlying these effects of PHG on synaptic plasticity remain to be determined. Thus the aim of this study was to examine the influence of PHG on synaptic plasticity in male AD rat model induced by bilateral central nervous system ventricle injections of beta amyloid 1-42 oligomers (Aβ1-42). The following parameters were measured: (1) number of intact pyramidal cells in hippocampal CA1 region by Nissl staining, (2) post synaptic density 95 (PSD-95), phosphorylated N-methyl-D-aspartate receptor-1(p-NMDAR1) and (3) phosphorylated Tau protein (p-Tau) by immunohistochemistry and western blot. In addition, the content of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Aβ1-42 lowered the number of intact pyramidal cells in hippocampal CA1 region. In contrast, treatment with PHG significantly elevated this cell number. Aβ1-42 significantly diminished protein expression levels of PSD-95 accompanied by elevated protein expression levels of p-NMDAR1 and p-Tau. PHG markedly increased protein expression levels of PSD-95, but significantly reduced protein expression levels of p-NMDAR1 and p-Tau. Further, Aβ1-42 markedly increased MDA content concomitantly with reduced activities of SOD and GSH-Px. PHG significantly decreased MDA content accompanied by elevated activities of SOD and GSH-Px. Data suggest that the protective effects of PHG on synaptic plasticity may involve inhibition of cytotoxicity-mediated by Aβ-1-42 administration and reduction of oxidant stress.

We present a coherent bichromatic laser system with low phase noise. An optical injection process is used to generate coherent laser beams with a frequency difference of 9.192 631 77 GHz using an electro-optical modulator. An optical phase-locked loop is then applied to reduce the phase noise. The phase noise of the beat note is -41, -81, -98, -83, and -95 dBrad 2 /Hz at the offset frequencies of 1 Hz, 100 Hz, 1 kHz, 10 kHz, and 1 MHz, respectively. Compared to a system that uses optical injection alone, the phase noise is reduced by up to 20-30 dB in the low-frequency range, and the intermodulation effect on the continuous atomic clock is reduced by an order of magnitude. This configuration can adjust the intensities and polarizations of the laser beams independently and reduce the phase noise caused by environmental disturbances and optical injection, which may be useful for application to atomic coherence experiments.

Herein, we report a conformation switching-based fluorescence sensing scheme using dipeptide-based amidothioureas (azapeptides) that contain a folded β-turn structure. Amidothiourea is equipped at its two termini with an electron acceptor and an electron donor or two fluorophores, such that it exhibits enhanced exciplex or excimer emission because of the turn structure in which the two termini are brought into close proximity; on the other hand, it exhibits a dramatic ratiometric fluorescence response upon anion binding to the thiourea moiety because of the resultant extended conformation of the anion binding complex.

Acute changes in select physiological parameters associated with cardiovascular physiology (systolic and diastolic blood pressure (BP) and heart rate (HR)), pulmonary function (FVC, FEV1, and exhaled CO and NO) and adverse events were measured in 105 clinically confined subjects who were randomized into groups that either completely or partially switched from conventional cigarettes to e-cigarettes or completely discontinued using tobacco and nicotine products altogether. Use of the e-cigarettes for five days under the various study conditions did not lead to higher BP or HR values, negative respiratory health outcomes or serious adverse health events. Reductions in BP and HR vital signs were observed in most of the participants that either ceased tobacco and nicotine products use altogether or switched completely to using e-cigarettes. Pulmonary function tests showed small but non-statistically significant improvements in FVC and FEV1 measurements in most use groups. Statistically significant (p < 0.05) benefits associated with smoking reduction were also noted in exhaled CO and NO levels. All study products were well tolerated. The study findings suggest that there are potential cardiovascular and pulmonary function benefits when smokers switch to using e-cigarette products. This further reinforces the potential that e-cigarettes offer smokers seeking an alternative to conventional tobacco products., (Copyright © 2017 Fontem Ventures B.V. Published by Elsevier Inc. All rights reserved.)

Yin Yang 2 (YY2) is a multifunctional zinc-finger transcription factor that belongs to YY family. Unlike the well-characterized YY1, our understanding regarding the biological functions of YY2 is still very limited. Here we found for the first time that in contrast to YY1, which had been reported to be oncogenic, the expression level of YY2 in tumor cells and/or tissues was downregulated compared with its expression level in the normal ones. We also demonstrated that YY2 exerts biological function contrary to YY1 in cell proliferation. We elucidated that YY2 positively enhances p21 expression, and concomitantly, its silencing promotes cells to enter G2/M phase and enhances cell proliferation. Furthermore, we found that YY2 regulation on p21 occurs p53-dependently. Finally, we identified a novel YY2 binding site in the promoter region of tumor suppressor p53. We found that YY2 binds to the p53 promoter and activates its transcriptional activity, and subsequently, regulates cell cycle progression via p53/p21 axis. Taken together, our study not only identifies YY2 as a novel tumor suppressor gene that plays a pivotal role in cell cycle regulation, but also provides new insights regarding the regulatory mechanism of the conventional p53/p21 axis., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.