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Spinal cord injury entails a high risk of major disability, but there is still no effective treatment for this condition. This study aims to explore the neuronal apoptosis after spinal cord injury, which is a key component of secondary injury processes, and plays a critical role in the development of neurological dysfunction.We studied the expression of the E3 ubiquitin ligase Triad1 and its interaction with p53 in the spinal cord after a spinal cord contusion injury in rats. We explored the regulation function of Triad1 to the neuronal apoptosis through p53-caspase3 pathway in primary neurons.Triad1 was markedly up-regulated in the grey matter one day after injury, and the distribution and time point of Triad1 expression correlated with the presence of apoptotic neurons. Co-immunoprecipitation experiments further demonstrated that Triad1 interacted with p53 after spinal cord injury. Specific siRNA and overexpression plasmids for Triad1 were transfected into primary neurons, and the expression of both p53 and caspase3 was altered following the change of Triad1.These findings indicate that Triad1 is involved in regulating the pathological process of neuronal apoptosis mediated by p53-caspase3 pathway after spinal cord injury.

Cordyceps cicadae, an entomopathogenic fungus, is a source of traditional Chinese medicine in China. Due to the low yield of wild C. cicadae, artificial cultivation approaches will be needed to meet the increasing market demand. Using bioreactor culture can increase mass production and the abundance of the active component, N6‐(2‐hydroxyethyl)‐adenosine (HEA). Here, we describe a safety assessment for a novel mycelium preparation method. Many studies have confirmed the safety of C. cicadae mycelia. However, the acute safety pharmacology of the C. cicadae enriched with the high HEA (3.90 mg/g) compound has not been evaluated. This study evaluated the central nervous system (CNS), cardiovascular system, and respiratory system in ICR male mice via oral gavage administration. For each requested item, two batches of eight mice tested on a vehicle (0.5% carboxymethyl cellulose, CMC) and C. cicadae mycelia (1,000 mg/kg) were performed. The heart rate at 60 min for the vehicle and C. cicadae mycelium treatment was 700.3 ± 55.4 and 603.0 ± 42.3 bpm, respectively (p = .4279). For echocardiographic analysis, the LV mass of the vehicle and drug treatment was 86.7 ± 6.4 and 80.2 ± 7.7, respectively (p = .0933). In the respiratory test, the tidal volume of the vehicle and drug treatments was 0.11 ± 0.01 and 0.14 ± 0.01 at 60 min, respectively (p = .4262). These results demonstrate that the oral administration of HEA‐enriched C. cicadae mycelia is safe for the CNS, cardiovascular, and respiratory systems.

In significant contrast to the tremendous research efforts mostly geared to addressing the severe hole accumulation at the back contact of a p-type Cu2O photocathode with a fluorine-doped tin oxide (FTO) substrate, sluggish electron transfer from an n-type Cu2O photoanode to a tin-doped indium oxide (ITO) substrate has been largely overlooked. To tackle this issue that has been reported to largely limit the photoelectrochemical performance of n-type Cu2O photoanodes at a low bias, the present contribution puts forward a strategy to introduce oxygen vacancies into the ITO substrate via an unprecedented yet facile electrochemical approach. Such defect engineering turns out to decrease the work function of the ITO substrate, which in turn approaches the conduction band extremum of n-Cu2O to highly efficiently extract the photoexcited electrons therein. Moreover, the dendritic growth of n-Cu2O is, in the meantime, interfered by the oxygen vacancy manifested as pinholes distributed over the ITO substrate, which is thereby crystallized into several small grains with augmented surface roughness that is in favor of the injection of the photoexcited hole into the electrolyte. Such facile interfacial charge-transfer kinetics leads to a significant cathodic shift amounting to 200 mV of the onset potential to 0 VAg/AgCl, whereat the n-Cu2O photoanode deposited on the defective ITO substrate delivers the maximum photocurrent density reaching 2 mA cm-2 and, more significantly, its applied bias photon-to-current efficiency (ABPE) reaches 1.1%, which is among the highest performance reported to date for a variety of state-of-the-art metal oxide-based photoanodes in the literature.

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8–20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with

Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

The aim of this trial was to evaluate the effects of an immunomodulatory supplement (OmniGen AF, OG; Phibro Animal Health Corp.) and heat stress on hormonal, inflammatory, and immunological responses of lactating dairy cows. Sixty multiparous Holstein cows were randomly assigned to 4 treatments in a 2 × 2 factorial arrangement using 2 environments: cooled using fans and misters, or noncooled, and 2 top-dressed feed supplements (56 g/d): OG or a placebo (CTL). Temperature-humidity index averaged 78 during the 8-wk trial. Blood was drawn to analyze cortisol, prolactin, and circulating tumor necrosis factor (TNF)-α and IL-10. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with hydrocortisone, prolactin, or lipopolysaccharide (LPS), individually or in several combinations, to assess induced proliferation and cytokine production. At d 52, 6 cows per treatment were injected i.v. with an LPS bolus (ivLPS) to assess hormone and cytokine responses. For cooled cows, feeding OG increased plasma cortisol concentration relative to CTL. Noncooled cows fed CTL had lower circulating TNF-α concentrations than noncooled-OG and cooled-CTL cows, with cooled-OG intermediate. Hydrocortisone+LPS-stimulated PBMC from OG cows tended to proliferate more than CTL. Relative to cooled cows, PBMC from noncooled cows produced more TNF-α and IL-10 when stimulated with LPS. Following ivLPS, cooled-OG cows had a greater cortisol response than the other treatments. In conclusion, OG supplementation enhanced cortisol release under basal condition and induced inflammation with cooling compared with CTL. This suggests that heat stress inhibits OG-mediated cortisol release. Heat stress seemed to enhance the inflammatory responses of PBMC from lactating cows. However, OG supplementation promoted PBMC proliferation under stress, or in the presence of hydrocortisone.

BACKGROUND Citation analysis can provide a historical perspective in the advancement of research, evolution, and areas of research. Taiwan exhibits rigorous academic and scientific activities in dentistry; however, based on its empirical contribution in research, there is no report in the literature analyzing the top-cited articles published by authors affiliated with Taiwan institutes. The purpose of this study was to analyze the citation characteristics of the top 100 most-cited articles published in dentistry with author(s) affiliated with Taiwan institutes. METHODS The Scopus database was used to search the qualified articles with authors from Taiwan published in journals. The bibliometric parameters, including year of publication, study design, research fields, citation half-life, self-citation, institute of origin, and international collaboration were analyzed. Multivariable linear regression in generalized linear model was used to find associate factors related to trends of citation counts. RESULTS The top 100 most-cited articles were determined by analyzing 7667 articles from the Scopus database. The steadily increasing trends were observed in the number and percentage of articles of author(s) affiliated with Taiwan institutes to the world. The most common study design was the in vitro research (55 %). The majority citation half-life is 3-5 and 6-8 years, and self-citation counts were between one to five times (n = 26). The percentage of international collaboration of these most-cited articles was 32%, and the main collaboration country was the United States. By using multivariable linear regression in the generalized linear model, the associated factors, study design, and self-citation were significantly associated with the escalating trends of citation counts. CONCLUSION This is the first study that provides valuable information in the dentistry regarding the academic activity, and empirical contribution of author(s) affiliated with Taiwan institutes in the world. The trends of citation characteristics were significantly correlated with study design and self-citation of these articles.

Purpose This study aims to examine the psychological distress experienced by unemployed and furloughed hospitality workers during the COVID-19 crisis and further investigate how this distress affects their career change intentions. Design/methodology/approach Derived from a sample of 607 unemployed and furloughed hospitality workers during the COVID-19 pandemic, the data for this research are analyzed using structural equation modeling. Findings This study reveals that unemployed and furloughed hospitality workers are financially strained, depressed, socially isolated and panic-stricken due to the pandemic’s effects. These effects lead to impaired well-being and an increased intention to leave the hospitality industry. Female and younger employees are impacted to a greater extent, while furloughed workers received fewer impacts compared to their laid-off compatriots. Research limitations/implications This study suggests that lockdown restrictions need to be implemented more deliberately, and the psychological well-being of the hospitality workforce deserves more immediate and continuing attention. It advises that hospitality businesses consider furloughs over layoffs when workforce reduction measures are necessary to combat the financial crisis. Originality/value This study adds to the current literature by examining the impact of the COVID-19 pandemic from the employee perspective. New insights are offered on the psychological toll of workforce reduction strategies during the financial fallout and how these distressing experiences affect career change intention.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further similar to 15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Thermal or photochemical 1,4-coupling reactions of butadiyne units can be employed to cross-link polymers. Poly(arylenebutadiynylene)s are solution-processable organic semiconducting polymers which...

Background Patients receiving hemodialysis (HD) often experience multiple symptoms concurrently and these symptoms may impact their quality of life. A valid and reliable tool is needed to assess the symptom distress of patients receiving HD in terms of the perspective of symptom clusters. Although many studies have explored symptom clusters related to patients receiving HD, the clusters formed had problems with overlapping, vagueness, lack of cluster-specificity, and difficulty in discerning their common mechanism under the cluster. Aims To develop reliable measurement tool to identify the symptom clusters of patients undergoing HD. Design A cross-sectional descriptive study. Methods To examine the physiological properties of the HD symptom distress (HSD) scale, 216 participants were recruited from a HD center of a medical university hospital in southern Taiwan from February 2019 to April 2019. Construct validity was evaluated by exploratory factor analysis (EFA), and the internal consistency and test–retest reliability were estimated by Cronbach’s alpha and intraclass correlation coefficient (ICC). Results The CVI value of the HSD was 0.89. The HSD scale was composed of five factors with 22 items, including insufficient energy/vitality, cardiac–pulmonary distress, sleep disturbance, musculoskeletal distress, and gastrointestinal distress, with factor loading ranging from 0.62 to 0.87, explaining 65.5% of the total variance. Cronbach’s alpha coefficient of the HSD total scale was 0.93, and five subscales ranged from 0.73 to 0.89. The test-retest reliability was 0.92 (p Conclusion / implication Theoretical testing from our study indicated that the HSD-22 scale had satisfactory validity and reliability. Therefore, this assessment tool can be employed to identify the symptom clusters of patients receiving HD in the clinical setting. Such identification enables healthcare professionals to provide interventions to release patients’ symptom distress efficiently.

Despite demonstrating higher photoluminescence quantum yield and better ambient and operational stability than organic–inorganic hybrid perovskites, all-inorganic perovskites encounter the problem of inferior film quality and interfacial electrical properties, which limits the resultant device performance. In this study, three polymers, P4a–c, bearing distinct pendant groups based on a similar conjugated group are synthesized and employed as an interlayer to modify the PEDOT:PSS/CsPbBr3 interface. Due to the pendant design, P4a–c possess deep-lying HOMO levels and high transparency across the visible range. The different structures of the pendant groups in P4a–c are shown to result in their different propensity in energy-level modulation and solid-state aggregation, which plays a non-trivial role in affecting the resulting device performance. Due to the more appropriate energy levels and better regulation of CsPbBr3 crystals, P4c with a polar bridge moiety is shown to better mediate the performance of the derived device. The P4c-mediated PeLED delivers six times enhanced luminance (Lmax, ∼36 000 cd m−2) and 3.6 times enhanced external quantum efficiency (EQE, 2.16%) as compared to the control device (∼6000 cd m−2, 0.60%). Notably, all the devices using P4a–c interlayers deliver a lower turn-on voltage than the control device, clearly revealing the positive role of P4a–c interlayers on diminishing the barrier across the associated interface to improve charge injection efficiency.

Stretchable electronics have received great attention in recent years because they are able to accommodate large mechanical deformation without damage to their electronic properties. These features are highly desirable for novel applications, including wearable devices, health-monitoring electronics, electronic skin, and artificial neural devices. A key factor in the area of stretchable electronics is the development of intrinsically stretchable polymer semiconductors. This review will survey different approaches that can significantly enhance the stretchability of polymer semiconductors without sacrificing their charge-transport properties. To develop stretchable polymer semiconductors, two approaches have been reported: (1) the engineering of the chemical structures of conjugated polymers; and (2) the physical blending of conjugated polymers in an elastomeric matrix. In addition to these two approaches, the influence of the fabrication process (e.g., solution shearing, nanoconfinement, and electrospinning) on the mechanical and electrical properties of polymer semiconductor films is also reviewed. In the final part, we will introduce novel applications of stretchable polymer semiconductors (e.g., electronic skin, artificial neural electronics, and self-healing polymer semiconductors) and the challenges facing these emerging technologies. This review provides a comprehensive introduction to the development of intrinsically stretchable polymer semiconductors covering molecular design, solution processes, and novel applications.

Background/Purpose Population aging and unequal accessibility of health care are increasingly important in developed countries. One strategy to overcome these issues is utilizing telemedicine, which is recently made possible technologically by the advancement of internet speed, high speed zooming cameras, and the information storages. In Taiwan, the telemedicine is granted legally by the amendment for Taiwan's Physician Act in 2018. Methods Kaohsiung Chang Gung Memorial Hospital (Kaohsiung CGMH) is the first hospital in Taiwan to provide the telemedicine service connecting to Cheng Kung Branch of Taitung Hospital since Nov 2018. Consultation services from Dermatology, ENT, and Ophthalmology have been delivered in the live-interactive and face to face module every week. Results Dermatology consultation comprises the majorities. In the first year, there were totally 426 dermatology consultation services. Eczema, fungal infections, and scabies infestation were the three most common diseases in the beginning. The disease diagnosis became more diverse after several months, including some ready-to-treat diseases pending correct diagnosis, such as pediculosis, psoriasis, and urticaria. Coupled with dermoscopic images, diseases such as hair loss, pediculosis capitis, skin tumor, and scabies, were diagnosed promptly. The subjective patient improvement rate was more than 75% year-round and the case closure rate was more than 85% year-round. Conclusion Teledermatology is a promising approach to serve the remote medical-underprivileged regions. The teledermatology is anticipated to help underserved regions, nursing homes, prisons, and in situations with severe pandemic infections, such as COVID-19.

BACKGROUND: Recent studies have suggested that cognitive-motor dual-task (DT) training might improve gait performance, locomotion automaticity, balance, and cognition in patients with Parkinson’s disease (PD). OBJECTIVE: We aimed to investigate the efficacy of cognitive-cycling DT training in patients with early-stage PD. METHODS: Participants were scheduled to perform cognitive tasks simultaneously with the cycling training twice per week for eight weeks for a total of 16 sessions during their on-states. Clinical assessments were conducted using the unified Parkinson’s disease rating scale (UPDRS), modified Hoehn and Yahr stage, Timed Up and Go (TUG) test, gait and cognitive performances under dual-task paradigm, the new freezing of gait questionnaire, Schwab and England Activities of Daily Living scale, 39-item Parkinson’s disease questionnaire, and cognitive performance. RESULTS: Thirteen eligible patients were enrolled in the study. The mean age was 60.64±5.32 years, and the mean disease duration was 7.02±3.23 years. Twelve PD patients completed 16 serial cognitive-cycling sessions for two months. After 16 sessions of training (T2), the UPDRS III scores improved significantly in both the off- and on-states, and TUG were significantly less than those at pretraining (T0). During both the single-task and the DT situations, gait performance and spatial memory cognitive performance significantly improved from T0 to T2. CONCLUSION: The present study demonstrated that cognitive-cycling DT training improves the motor functions, gait and cognitive performances of PD patients.

Background High blood pressure is common and comorbid with type 2 diabetes (T2D). Almost 50% of patients with T2D have high blood pressure. Patients with both conditions of hypertension (HTN) and T2D are at risk for cardiovascular diseases and mortality. The study aim was to investigate genetic risk factors for HTN in T2D patients. Methods This study included 999 T2D (cohort 1) patients for the first genome scan stage and 922 T2D (cohort 2) patients for the replication stage. Here, we investigated the genetic susceptibility and cumulative weighted genetic risk score for HTN in T2D patients of Han Chinese descent in Taiwan. Results Thirty novel genetic single nucleotide polymorphisms (SNPs) were associated with HTN in T2D after adjusting for age and body mass index (P value Conclusions A cumulative weighted genetic risk score composed of 14 SNPs is important for HTN, increased tendency of systolic blood pressure, and may contribute to HTN risk in T2D in Taiwan.

Background To investigate the association of dipeptidyl peptidase-4 inhibitors (DPP4is) treatment doses and tuberculosis (TB) in patients with diabetes. Methods We allocated participants into DPP4i users and non-users from the Longitudinal Health Insurance Database. A chi-square test and Wilcoxon's rank-sum test were used to analyze the baseline discrete variables and continuous variable, respectively. The incidence rate was calculated in 1,000 personyears. The hazard ratios (HRs) were adjusted using a multivariate Cox regression model. The effect of DDP4i dosage on TB was analyzed. The Kaplan-Meier method was used to assess the cumulative incidence curves with a log-rank test. Results We identified 6,399 DPP4i users and 6,399 non-users. The incidence rate of TB in DPP4i users and non-users was 22.2 and 16.2 per 1,000 person-years, respectively. The HR of TB for DPP4i users relative to non-users was 1.04 (P=0.89). Most of the analysis of factors such as the incidence rate, gender and diabetic comorbidities in our study were non-significant. The risk of developing TB in patients with over 20 average defined daily doses (DDDs) per year was increased by 2.19 times (P=0.048). Conclusions In our long-term nationwide population-based cohort study, higher doses of DPP4i (20 average DDDs) could increase TB infection risk in patients with diabetes. To pay more attention to this kind of diabetic patients with DPP4i treatment will be more important for the public health issue of TB prevention.

The rapid development of Internet of Things and big data has made the conventional storage devices face the need of reforming. Rather than using electrical pulses to store data in one of two states, photomemory exploiting optical stimulation to store light information emerges as a revolutionary candidate for the optoelectronic community. However, fully optically driven photomemory with fast data transmission speed and outstanding energy saving capability suffers from less exploration. Herein, a transistor-type photomemory using a 2D Cs2Pb(SCN)2Br2/polymer hybrid floating gate is explored and three host polymers, polystyrene, poly(4-vinylphenol), and poly(vinylpyrrolidone) (PVP), are investigated to understand the relationship between polymer matrix selection and memory performance. All devices show a photoinduced recovery memory behavior but with two distinctly different photomemory behaviors. In addition to the demonstration of a regular nonvolatile photomemory showing a high on/off ratio of >106 over 104 s, an unusual fully optically driven memory behavior is intriguingly accomplished in the Cs2Pb(SCN)2Br2/PVP photomemory. Using white light as the driver of programming and a blue laser as the main performer of erasing, this device can be switched between two distinguishable states and possesses acceptable data discriminability, as evidenced by its fully optically driven writing (programing)-reading-erasing-reading switching function that shows an on/off current ratio of 103. This study not only presents the first 2D perovskite-based photomemory but also shows a novel fully optically driven memory that has been rarely reported in the literature.

To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP4i) for Klebsiella pneumoniae (KP) pneumonia in patients with diabetes. Patients newly diagnosed with type 2 diabetes from 2009 to ...

BACKGROUND: Myocardial mitochondrial dysfunction is the leading cause of chronic heart failure (CHF). Increased reactive oxygen species (ROS) levels, disruption of mitochondrial biogenesis and mitochondrial Ca(2+)([Ca(2+)]m) homeostasis and reduction of the mitochondrial membrane potential (ΔΨm) cause myocardial mitochondrial dysfunction. Therefore, treating CHF by targeting mitochondrial function is a focus of current research. For the first time, this study investigated the effects of the strong antioxidant pyrroloquinoline quinone (PQQ) on mitochondrial function in a cardiac pressure overload model, and the mechanism by which PQQ regulates [Ca(2+)]m homeostasis was explored in depth. METHODS: After transaortic constriction (TAC), normal saline and PQQ (0.4, 2 and 10 mg/kg) were administered intragastrically to Sprague Dawley (SD) rats for 12 weeks. In vitro, neonatal rat left ventricle myocytes (NRVMs) were pretreated with 200 nm angiotensin II (Ang II) with or without PQQ (1, 10 and 100 μM). Rat heart remodelling was verified by assessment of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels (qRT-PCR), cell surface area (wheat germ agglutinin (WGA) staining in vivo and α-actin in vitro) and echocardiography. Myocardial mitochondrial morphology was assessed by transmission electron microscopy. Western blotting was used to assess mitochondrial biogenesis [peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and transcription factor A, mitochondrial (TFAM)]. The ΔΨm was determined by tetraethyl benzimidazolyl carbocyanine iodide (JC-1) staining and flow cytometry, and ROS levels were measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) and MitoSOX Red staining. [Ca(2+)]m was measured by isolating rat mitochondria, and mitochondrial Ca(2+) channel proteins [the mitochondrial Na(+)/Ca(2+) exchanger (NCLX) and mitochondrial Ca(2+) uniporter (MCU)] were detected by Western blot. RESULTS: In vivo and in vitro, PQQ pretreatment improved pressure overload-induced cardiac remodelling and cell hypertrophy, thus preventing the occurrence of CHF. PQQ also prevented mitochondrial morphology damage and reduced the PGC-1α and TFAM downregulation caused by TAC or Ang II. In addition, in NRVMs treated with Ang II + PQQ, PQQ regulated ROS levels and increased the ΔΨm. PQQ also regulated [Ca(2+)]m homeostasis and prohibited [Ca(2+)]m overloading by increasing NCLX expression. CONCLUSIONS: These results show that PQQ can prevent [Ca(2+)]m overload by increasing NCLX expression and thereby reducing ROS production and protecting the ΔΨm. At the same time, PQQ can increase PGC-1α and TFAM expression to regulate mitochondrial biogenesis. These factors can prevent mitochondrial dysfunction, thereby reducing cardiac damage caused by pressure overload and preventing the occurrence of CHF.

To explore the clinical effect and adverse reactions of Strychnos nux-vomica in bortezomib-induced peripheral neuropathy (BIPN) of patients with multiple myeloma (MM).A total of 19 MM patients with BIPN were enrolled and Nux Vomica Capsule (NVC, 0.4 g, thrice daily) were orally administrated for 30 days. Comparative analysis on parameters between pre- and post-therapy, including peripheral neuropathy (PN) grade, neurotoxicity score, Chinese medicine (CM) syndrome score, total neuropathy score (TNS), coagulation function, and serum nerve growth factor (NGF) levels were conducted. The adverse events were monitored.In BIPN of MM patients who received NVC, PN grade was lowered, neurotoxicity score was obviously decreased (P⩽0.01), and both CM syndrome score and TNS were remarkably decreased (P0.01). After the therapy, activated partial thromboplastin time was prolonged (P0.01) and fibrinogen was declined (P0.05), showing improvement in the hypercoagulable state of patients. No significant difference of NGF recovery degrees was detected between pre- and post-therapy (P0.05). No evident adverse reactions were observed during the course of treatment.Strychnos nux-vomica L. has significantly effect with a good safety in treatment of BIPN in MM patients.

This study evaluated street trees’ potential for energy recovery and greenhouse gas (GHG) mitigation/emissions throughout their lifespans. Trees can mitigate GHG emissions as a result of CO2 uptake during growth; but GHGs are emitted when the branches and/or leaves are used as compost or fuel for energy production at the end of its life. A 41‐year period (1976–2017) of the street trees along the sidewalks of the Tianliao river in Keelong city in Taiwan was taken a case study. The results showed that planting street trees helps mitigate climate change by reducing total GHG emissions (15 661 t CO2‐eq) and producing an amount of renewable energy (5.9×106 kWh), that is around 1% of the renewable energy generated by 24 waste‐to‐energy plants in Taiwan. The GHG mitigation during the lifespans of street trees can efficiently compensate for the GHG emissions that occur during end‐of‐life treatment (including both incineration and composting). On average, around 40 t CO2‐eq of GHG mitigation would be achieved by planting a street tree. The cost‐effectiveness analysis showed that US$223 992 were saved over the study period due to the reduction in carbon tax achieved by the mitigation of GHGs. The results of this study should increase awareness on the importance of planting trees and managing wood waste in environmental protection strategies for mitigating climate change. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.

Background Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. Materials and Methods In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. Results Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88–1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18–4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88–3.95]) but not in cancer-free women (HR = 0.91 [0.79–1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). Conclusion These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. Implications for Practice Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.

This study used the torrefaction method to innovatively integrate spent coffee grounds (SCG) and silver skin into biofuels. The biofuels were dried, pelletized, and torrefied at 300 °C for 3 h. The mass yields and energy yields of the biofuels ranged from 41% to 43% and from 52% to 58%, respectively. The high heat value (HHV) range of the biofuels (24.23–27.28 MJ/kg) was higher than that reported in previous studies. The results revealed that an increase in the percentage of silver skin increased the hygroscopicity of the biofuels, which was unfavorable for storage. On average, the weight increased by 0.24–0.57 wt% with a 10 wt% increase of silver skin in the biofuels. The biofuels had zero sulfur and chlorine content and thus would be cleaner energy sources than coal. The elemental compositions of the biofuels were similar to that of lignite with 0.063–0.070 H/C and 0.34–0.44 O/C ratios. The sample most similar to coal, based on heating value, element content, proximate analysis results, and combustion characteristics, exhibited 62% similarity. Integrating silver skin with other materials may be unsuitable for biofuels, but it is helpful for reducing the environmental burden of landfilling or incineration.

Perovskite light-emitting diode (PeLED) has been vigorously developed in recent years. As it has demonstrated good performance on the rigid substrates, the next important direction of PeLED is its integration with stretchable components to realize stretchable, responsive device. Here, we describe a facile fabrication of stretchable perovskite light-emissive touch-responsive devices (PeLETDs) by utilizing highly transparent and conductive polyurethane/silver nanowires (PU/AgNWs) as the electrode. Meanwhile, a stretchable tricomposite perovskite emissive layer was developed by blending a small amount of poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) with CsPbBr

Nonmotor symptoms (NMSs) severely affect the daily quality of life of patients with Parkinson’s disease (PD). Although many studies have documented the clinical characteristics of NMSs in PD patients, some issues remain unaddressed. The severity and gender distribution of NMSs in Asian and the Western patients differ. The correlations between clinical characteristics and NMS manifestations remain unclear. We studied these relationships in a large cohort of Taiwanese PD patients. Patients with PD were recruited from the outpatient clinic of a tertiary medical center and evaluated with standardized assessment protocols, including the NonMotor Symptoms Scale (NMSS), Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, Mini-Mental Status Examination, and Montreal Cognitive Assessment. Among 820 patients enrolled, 41.8% were female. The prevalence of the NMSs was 96.5%, with attention/memory (79.51%) being the most frequently involved domain. The mean severity score on the NMSS was 36.48 ± 34.30. Male patients reported higher NMS prevalence and severity than female patients, mostly in the gastrointestinal tract and urinary domains. We found that the severity of NMSs was correlated with disease duration, UPDRS Part III score, and H&Y stage. Although they exhibited similar NMS prevalence, Taiwanese PD patients reported less intense NMSs compared with those reported by Western patients. Furthermore, the NMS items our patients emphasized and gender discrepancies were distinct from those in Western studies.

Aim To evaluate the effect of mean HbA1c on the correlation between HbA1c variability and all-cause mortality, and the risks associated with different levels of HbA1c and glycaemic control status in patients with type 2 diabetes. Materials and methods Patients with type 2 diabetes and at least three HbA1c measurements within 12-24 months were included. HbA1c variability score, coefficient of variation (CV) and standard deviation (SD) were used to evaluate variability. A variability score of 50 was set as a cutoff to define low and high variability. Results A total of 4216 patients were included, of whom 1196 died during the observation period (11.1 ± 3.2 years). All-cause mortality increased with HbA1c variability score and the quartiles of HbA1c CV and SD. The strength of this association was attenuated after adjustment for mean HbA1c, and the risks associated with HbA1c variability and glycaemic control status were similar. The highest associated risk was observed with an HbA1c variability score of >50 and mean HbA1c of ≥7.5%. Mortality risk was significantly higher with a mean HbA1c of ≤6.0% and >8.5% and of ≤6.0% and >8.0% for low and high HbA1c variability, respectively. Conclusions Mean HbA1c contributed to the correlation between HbA1c variability and all-cause mortality. The risks associated with HbA1c variability and glycaemic control status were similar. The relationship between mean HbA1c and mortality presented a J-shaped distribution for both low and high HbA1c variability.

High dietary glycaemic index (GI) and glycaemic load (GL) may increase cancer risk. However, limited information was available on GI and/or GL and head and neck cancer (HNC) risk. We conducted a pooled analysis on 8 case-control studies (4081 HNC cases; 7407 controls) from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of HNC, and its subsites, from fixed- or mixed-effects logistic models including centre-specific quartiles of GI or GL. GI, but not GL, had a weak positive association with HNC (ORQ4 vs. Q1 = 1.16; 95% CI = 1.02–1.31). In subsites, we found a positive association between GI and laryngeal cancer (ORQ4 vs. Q1 = 1.60; 95% CI = 1.30–1.96) and an inverse association between GL and oropharyngeal cancer (ORQ4 vs. Q1 = 0.78; 95% CI = 0.63–0.97). This pooled analysis indicates a modest positive association between GI and HNC, mainly driven by laryngeal cancer.

To address the longstanding issue of conventional supercapacitors, viz. their energy and power deliveries are largely attenuated by the poor packing density of particularly the active electrodes, an ultracompact yet porous monolithic electrode is put forward in the present study. Particularly, it is built on electroactive α′-NaxV2O5 with the areal mass loading amounting to 33.24 mg cm−2 densely packed into a 330-μm-thick carbon cloth and more importantly, with a hierarchical meso-/nano-pore structure in favor of the ion transport throughout this 330 μm-thick α′-NaxV2O5/CC heavy electrode. In such context, a series of superior performances including the areal, gravimetric and volumetric capacitances reaching 12.47 F cm−2, 375.2 F g−1 and 377.93 F cm−3, and the energy and power densities amounting to 1.38 mW h cm−2 and 34.1 mW cm−2 are successfully delivered by this compact monolith at the electrode- and device-level, respectively, altogether outperforming significantly those of additional modern and promising electrodes and energy storage devices reported in the literature.

All-inorganic perovskite solar cells (PVSCs) have drawn increasing attention because of their outstanding thermal stability. However, their performance is still inferior than the typical organic-inorganic counterparts, especially for the devices with p-i-n configuration. Herein, we successfully employ a Lewis base small molecule to passivate the inorganic perovskite film, and its derived PVSCs achieved a champion efficiency of 16.1% and a certificated efficiency of 15.6% with improved photostability, representing the most efficient inverted all-inorganic PVSCs to date. Our studies reveal that the nitrile (C-N) groups on the small molecule effectively reduce the trap density of the perovskite film and thus significantly suppresses the non-radiative recombination in the derived PVSC by passivating the Pb-exposed surface, resulting in an improved open-circuit voltage from 1.10 V to 1.16 V after passivation. This work provides an insight in the design of functional interlayers for improving efficiencies and stability of all-inorganic PVSCs., There has been a hot competition to optimize the device performance for all-inorganic perovskite solar cells. Here Wang et al. employ a Lewis base molecule to suppresses the non-radiative recombination in the inverted device and achieve a champion efficiency of 16.1%.

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene–sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency

Context Osteoporosis is a degenerative bone disease in aging men and women. MiRNAs associated with progressive bone loss in osteoporosis had not been clearly demonstrated. Objective The evaluation of the differentially expressed miRNAs in the bone tissue and serum of osteoporotic women with aging. Methods MiRNAs GeneChip and real-time PCR were used to screen differently expressed miRNAs in bone tissues of 21 osteoporotic women ages 60–69 years and 80–89 years. Identified miRNAs were detected in the serum of the validation cohort, which consisted of 14 healthy premenopausal women and 86 postmenopausal women with osteopenia or osteoporosis. MiR-181c-5p and miR-497-5p expression were validated in aging and OVX mice models, and osteoblasts. Their role in osteogenesis was validated in vitro. Results Twenty-four miRNAs showed the highest differential expression in bone tissues of osteoporotic women in initial screening. Among them, four miRNAs were identified both in the bone tissue and serum in the validation cohort. The levels of miR-181c-5p and miR-497-5p were decreased in the serum of postmenopausal women with osteopenia or osteoporosis, but increased in subjects treated with bisphosphonate plus calcitriol. MiR-181c-5p and miR-497-5p were significantly downregulated in the bone tissue of aging and OVX mice models, and upregulated during the osteogenic differentiation of hFOB1.19 and MC3T3-E1 cells. Overexpression of miR-181c-5p and miR-497-5p promoted the differentiation and mineralization of osteoblasts. Conclusions MiR-181c-5p and miR-497-5p are involved in bone metabolism and associated with progressive bone loss of due to osteoporosis, suggesting that circulating miR-181c-5p and miR-497-5p might act as potential biomarkers for monitoring the effects of antiosteoporotic therapies or the diagnostic approach.

We evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72–0.78), 0.64 (0.60–0.68), and 0.78 (0.75–0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65–0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.

The aim of this study was to investigate the effects of local (LIPC) and remote (RIPC) ischemic preconditioning on sprint interval exercise (SIE) performance. Fifteen male collegiate basketball players underwent a LIPC, RIPC, sham (SHAM), or control (CON) trial before conducting six sets of a 30-s Wingate-based SIE test. The oxygen uptake and heart rate were continuously measured during SIE test. The total work in the LIPC (+2.2%) and RIPC (+2.5%) conditions was significantly higher than that in the CON condition (p &lt, 0.05). The mean power output (MPO) at the third and fourth sprint in the LIPC (+4.5%) and RIPC (+4.9%) conditions was significantly higher than that in the CON condition (p &lt, 0.05). The percentage decrement score for MPO in the LIPC and RIPC condition was significantly lower than that in the CON condition (p &lt, 0.05). No significant interaction effects were found in pH and blood lactate concentrations. There were no significant differences in the accumulated exercise time at ≥80%, 90%, and 100% of maximal oxygen uptake during SIE. Overall, both LIPC and RIPC could improve metabolic efficiency and performance during SIE in athletes.

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

Traumatic brain injury (TBI) represents a major cause of morbidity and disability and is a risk factor for developing neurodegenerative diseases, including Alzheimer’s disease (AD). However, no effective therapies are currently available for TBI-induced AD-like disease. Endocannabinoids are endogenous lipid mediators involved in a variety of physiological and pathological processes. The compound 2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid with profound anti-inflammatory and neuroprotective properties. This molecule is predominantly metabolized by monoacylglycerol lipase (MAGL), a key enzyme degrading about 85% of 2-AG in the brain. Studies using animal models of inflammation, AD, and TBI provide evidence that inactivation of MAGL, which augments 2-AG signaling and reduces its metabolites, exerts neuroprotective effects, suggesting that MAGL is a promising therapeutic target for neurodegenerative diseases. In this short review, we provide an overview of the inhibition of 2-AG metabolism for the alleviation of neuropathology and the improvement of synaptic and cognitive functions after TBI.

Purpose Low back pain (LBP) is a long-lasting and chronic symptom without any exact cause. This study attempts to propose a new staging system based on the original grading system combined with pathological results and clinical symptoms to better clarify the dynamic evolution of LBP related to cartilage degeneration during facet joint osteoarthritis (FJOA). To explore a potential target for diagnosis, treatment, and drug intervention of facet joint osteoarthritis related LBP via protecting chondrocytes. Materials and methods All the facet joints were divided into 4 groups according to our new degenerative staging system based on Weishaupt grade, CT and MRI. Collect the facet joint samples from patients whom suffered lumbar fusion surgery for lumbar disc herniation. Molecular biology experiments were used to explore the effect of Wnt16 on the degeneration of facet joints. Micro-CT examination and pain stimulation test checked the biological function of Wnt16 in rats. Results Wnt16 was significantly increased and more aggregated in the facet joint chondrocytes in the Phase III and Phase IV, which is consistent with the pathological findings of cartilage degeneration (OARSI). We found that Wnt16 participated in the regulation of FJOA via Wnt/β-catenin pathway in vitro, which was inhibited by specific inhibitor DKK1. The rats, rich expressed Wnt16, showed higher paw withdrawal thresholds and prolonged paw withdrawal latency to FJOA related LBP. Micro-CT examination for the lumbar spine of rats showed Wnt16 protected the chondrocytes from FJOA. Conclusions This study defined a new staging system for LBP related cartilage degeneration of facet joint based on the original grading system combined with pathological results and clinical symptoms. Wnt16 is expected to be a potential target for treatment of FJOA via protecting chondrocytes.

Chunghwa Telecom has established an Internet of Things (IoT) smart platform embedded with telephone access service (TAS) to allow IoT applications directly interacting with phones. This paper proposes an in-service PBX (Private Branch Exchange) surveillance approach based on the TAS APIs. A service surveillance application for enterprises' PBXs and the self-care portal for the service management are implemented. The application involves the design of surveillance method, the schedule of monitor calls, the detection of service status, and the notification of events and alerts. The real-case example demonstrates the effectiveness of the proposed in-service surveillance approach.

This paper describes the latest development of a W-band 90 nm-CMOS receiver chip that is suitable for use in radio-astronomical multi-pixel imaging arrays and other broadband scientific instruments. This circuit includes an RF-low-noise amplifier (LNA), mixer, intermediate-frequency amplifier (IF-Amp), local-oscillator (LO) tripler, and driving amplifier. With a tripler integrated into the circuit, the incoming 80–110 GHz spectrum can be directly down-converted to 2–32 GHz by the applied 26 GHz LO signal. The system architecture will be presented, with the corresponding sub-circuits discussed in detail. In the on-wafer measurement at room temperature, this receiver has around 10 dB gain and 15 dB noise figure across the whole frequency range, with 400 mW power dissipation under 1.8 V DC bias. By adding a compound-semiconductor LNA in front of this CMOS receiver chip, compact low-noise receiver modules can be easily constructed and deployed.

Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

Introduction: Aberrant Wnt signalling, regulating cell development and stemness, is observed in many cancer entities. Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated to lung cancer susceptibility. Aim: To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent. Methods: Odds ratios (OR) were estimated for genomic variants assigned to the genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2 and other lung cancer-related genes. Logistic regression models with variable selection were trained, validated and tested to predict lung cancer. Further, decision trees were created to investigate variant x variant interaction. All analyses were performed for overall lung cancer and for subgroups. Results: No association with overall lung cancer was observed, but within the subgroups of ever smokers (e.g. maker rs2722278 SFRP4; OR=1.20; 95%-CI: 1.13-1.27; p=5.6 10-10) and never smokers. Although predictability is poor, AhR/Wnt-variants are unexpected overrepresented in optimized prediction scores for overall lung cancer and for small cell lung cancer. Remarkable, the score for never-smokers contained solely two AhR/Wnt-variants. The optimal decision tree for never smokers consists of 7 AhR/Wnt-variants and only two lung cancer variants, no assigned to any CHRN gene. Conclusions: The role of variants belonging to Wnt/AhR-pathways in lung cancer susceptibility may be underrated in main-effects association analysis. Complex interaction patterns in individuals of European descent have moderate predictive capacity for lung cancer or subgroups thereof, especially in never smokers.

Objective: The study aims to investigate the association of total bilirubin with all-cause and cause-specific mortality in the general population.Methods: A total of 37,234 adults from the United States National Health and Nutrition Examination Survey 1999–2014 were enrolled. Baseline levels of total bilirubin associated with risk of mortality were evaluated on a continuous scale (restricted cubic splines) and by quartile categories with Cox regression models.Results: Higher levels of total bilirubin was positively associated with an increased risk of all-cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.46–1.72; p < 0.001]. Compared with individuals with the lowest quartile of bilirubin, the multivariable adjusted hazard ratio for all-cause mortality was 1.25 (1.14–1.37) for individuals in the highest quartile. Restricted cubic splines indicated that the association was non-linear in cardiovascular mortality and cancer mortality while linear in all-cause mortality.Conclusions: Total bilirubin was associated with all-cause and cause-specific mortality in the general population.

Background and purpose The purpose of our study was to analyse endovascular treatment (EVT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) during the pandemic and post-epidemic periods. Methods Patients with AIS-LVO of the anterior circulation who underwent EVT were enrolled. According to the times of Wuhan closure and reopening, patients were divided into a pre-pandemic group (from November 8, 2019, to January 22, 2020), pandemic group (from January 23, 2020, to April 8, 2020) and post-epidemic group (from April 9, 2020, to June 24, 2020). The primary endpoints were the time delay among symptom onset to arriving hospital door, to groining puncture and to vascular reperfusion. Secondary endpoints were the functional outcomes evaluated by 90-day modified Rankin scale (mRS) score. Results In total, the times from onset to reperfusion (OTR, median 356 min vs. 310 min, p = 0.041) and onset to door (OTD, median 238 min vs. 167 min, p = 0.017) were prolonged in the pandemic group compared to the pre-pandemic group, and the delay continue in the post-epidemic period. In the subgroup analysis, the time from door to imaging (DTI) was significantly prolonged during the pandemic period. Interestingly, the prolonged DTI was corrected in the directly admitted subgroup during post-epidemic period. In addition, the functional outcomes showed no significant differences across the three periods. Conclusions Total time and prehospital time were prolonged during the pandemic and post-epidemic periods. Urgent public education and improved in-hospital screening processes are necessary to decrease time delays.

In a population-based case control study of testicular germ cell tumors (TGCT), we reported a strong positive association between serum levels of Wolff's Group 1 (potentially estrogenic) polychlorinated biphenyl (PCBs) and risk of TGCT, and the observed associations were similar for both seminoma and non-seminoma. While the observed specific associations between TGCT and Wolff's Group 1 PCBs cannot be easily explained by bias or confounding, a question can still be asked, that is, could the relationship between PCBs and TGCT differ by age at diagnosis? PCBs tend to bioaccumulate, with more heavily chlorinated PCB congeners tending to have longer half-lives. Half-lives of PCB congeners were reported ranging from 4.6 years for PCB-28 to 41.0 years for PCB-156. The half-life for the heavy PCB congeners (17.8 years) was found to be approximately twice that for the light PCBs (9.6 years) in early studies. Therefore, the same PCB concentration measured in a 20-year-old vs. a 55-year-old is unlikely to represent the same lifetime PCB exposure or type of PCB exposure. In this analysis, we stratified the data by median age of diagnosis of TGCT and further stratified by histologic type of TGCT (seminoma vs non-seminoma) to explore if the risk of TGCT associated with PCB exposures differs by age.

The low sensitivity (α4)3(β2)2 (LS) and high sensitivity (α4)2(β2)3 (HS) nAChR isoforms may contribute to a variety of brain functions, pathophysiological processes, and pharmacological effects associated with nicotine use. In this study, we examined the contributions of the LS and HS α4β2 nAChR isoforms in nicotine self-administration, withdrawal symptoms, antinociceptive and hypothermic effects. We utilized two nAChR positive allosteric modulators (PAMs): desformylflustrabromine (dFBr), a PAM of both the LS and HS α4β2 nAChRs, and CMPI, a PAM selective for the LS nAChR. We found that dFBr, but not CMPI, decreased intravenous nicotine self-administration in male mice in a dose-dependent manner. Unlike dFBr, which fully reverses somatic and affective symptoms of nicotine withdrawal, CMPI at doses up to 15 mg/kg in male mice only partially reduced nicotine withdrawal-induced somatic signs, anxiety-like behavior and sucrose preference, but had no effects on nicotine withdrawal-induced hyperalgesia. These results indicate that potentiation of HS α4β2 nAChRs is necessary to modulate nicotine's reinforcing properties that underlie nicotine intake and to reverse nicotine withdrawal symptoms that influence nicotine abstinence. In contrast, both dFBr and CMPI enhanced nicotine's hypothermic effect and reduced nicotine's antinociceptive effects in male mice. Therefore, these results indicate a more prevalent role of HS α4β2 nAChR isoforms in mediating various behavioral effects associated with nicotine, whereas the LS α4β2 nAChR isoform has a limited role in mediating body temperature and nociceptive responses. These findings will facilitate the development of more selective, efficacious, and safe nAChR-based therapeutics for nicotine addiction treatment.

Objectives To evaluate the long-term cognitive or neuropsychiatric outcomes and potential risk factors associated with prolonged cognitive deficits or neuropsychiatric symptoms in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods In this cohort follow-up study, patients with a definitive diagnosis of anti-NMDAR encephalitis from the inpatient of West China Hospital between June 2012 and December 2017 were included and underwent a prospective cognitive and neuropsychiatric assessment every 3 months by cognitive impairment rating scale, Neuropsychiatric Inventory (NPI) and/or Montreal Cognitive Assessment. Results Up to 97.5% patients had severe cognitive deficits and neuropsychiatric symptoms in acute phase. Decreasing proportion of patients with prolonged cognitive deficits was observed and time dependent. At 2 years' follow-up, 7.8% of patients with cognitive deficits were unable to complete some previous activities or return to work. The risk factors associated with persistent cognitive deficits included age of disease onset over 40 years old (HR, 1.77; 95% CI, 1.11-2.82; P = .01) and with clinical relapses (HR, 2.22; 95% CI, 1.21-4.09; P = .02). The predictors of prolonged neuropsychiatric symptoms included clinical relapses (HR, 2.79; 95% CI, 1.21-6.43; P = .02). Among the 12 neuropsychiatric symptoms of NPI, irritability was shown as the most prevalent and persistent. Conclusions Combined cognitive and neuropsychiatric assessment and intervention are essential elements of comprehensive care of anti-NMDAR encephalitis.

Certificate validation in Secure Sockets Layer or Transport Layer Security protocol (SSL/TLS) is critical to Internet security. Thus, it is significant to check whether certificate validation in SSL/TLS implementations is correctly implemented. With this motivation, we propose a novel differential testing approach that is based on the standard Request for Comments (RFC). First, rules of certificates are extracted automatically from RFCs. Second, low-level test cases are generated through dynamic symbolic execution. Third, high-level test cases, i.e., certificates, are assembled automatically. Finally, with the assembled certificates being test cases, certificate validations in SSL/TLS implementations are tested to reveal latent vulnerabilities or bugs. Our approach named RFCcert has the following advantages: (1) certificates of RFCcert are discrepancy-targeted, since they are assembled according to standards instead of genetics; (2) with the obtained certificates, RFCcert not only reveals the invalidity of traditional differential testing but also is able to conduct testing that traditional differential testing cannot do; and (3) the supporting tool of RFCcert has been implemented and extensive experiments show that the approach is effective in finding bugs of SSL/TLS implementations. In addition, by providing seed certificates for mutation approaches with RFCcert, the ability of mutation approaches in finding distinct discrepancies is significantly enhanced.