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  1. The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise
    Ando S, Fujimoto T, Sudo M, Watanuki S, Hiraoka K, Takeda K, et al.
    J Physiol, 2024 Feb;602(3):461-484.
    PMID: 38165254 DOI: 10.1113/JP285173
    Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.
  2. Fulltext Effect of the COVID-19 Pandemic on Medical Student Career Perceptions: Perspectives from Medical Students in China
    Cai CZ, Lin Y, Alias H, Hu Z, Wong LP
    Int J Environ Res Public Health, 2021 05 11;18(10).
    PMID: 34064814 DOI: 10.3390/ijerph18105071
    Our aim was to examine perceived occupational turnover intentions among medical students and the associated factors. A cross-sectional study using a Web-based survey was conducted. A total of 2922 completed responses were received (response rate 55.7%). A total of 58.4% (95% CI 56.6-60.2) reported high turnover intention (score of 7-15). The odds of higher total turnover score among the fifth-year students was nearly four times that of first-year students (OR = 3.88, 95% CI 2.62-5.73). Perception of the medical profession as not being of high social status and reputation significantly influenced high turnover intention scores (OR = 2.26, 95% CI 1.90-2.68). All three dimensions of the multidimensional scale of perceived social support (MSPSS) significantly predict turnover intention. Lower scores in the support from Significant Other (OR = 1.47, 95% CI 1.17-1.84), Family (OR = 1.47, 95% CI 1.18-1.83) and Friend (OR = 1.42, 95% CI 1.14-1.77) subscales were associated with higher turnover intention. Low score in the Brief Resilience Scale (BRS) was also associated with higher turnover intention (OR = 1.44, 95% CI 1.17-1.77). The findings shed light on the importance of changing public attitudes towards respecting the medical profession and improving the implementation of policies to protect the well-being of people in the medical profession.
  3. Fulltext Behavioural responses and anxiety symptoms during the coronavirus disease 2019 (COVID-19) pandemic in Japan: A large scale cross-sectional study
    Cai G, Lin Y, Lu Y, He F, Morita K, Yamamoto T, et al.
    J Psychiatr Res, 2021 Apr;136:296-305.
    PMID: 33631655 DOI: 10.1016/j.jpsychires.2021.02.008
    BACKGROUND: This study explored the behavioural responses and anxiety symptoms of the general adult population in Japan during the ongoing coronavirus disease 2019 (COVID-19) outbreak.

    METHODS: A web-based cross-sectional survey was conducted between 12th and May 13, 2020. Quota sampling was used to attain equal gender and age distributions representative of the Japanese population.

    RESULTS: A total of 4127 complete responses were analysed. Higher educational level (B = 0.045, p = 0.002) and household income (B = 0.04, p = 0.009) were associated with a higher increase in preventive measures when comparing before and after the state of emergency was declared. The highest reported social anxiety was a feeling of fear (65.6%), followed by embarrassment (43.8%), keeping infection a secret (41.3%), avoidance (41.3%), and stigma (25.5%). A total of 86.1% of the respondents reported moderate to severe anxiety. The partial least square-based structural equation modelling (PLS-SEM) revealed that being female has the greatest effect (B = 0.246, p 

  4. Fulltext Quality evaluation of compounds in leaves of six Taxus species based on UPLC-MS/MS and chemometrics
    Cai Q, Song Q, Jiang K, Lin Y, Zhang Y, Zhang J, et al.
    Front Chem, 2023;11:1193188.
    PMID: 37324558 DOI: 10.3389/fchem.2023.1193188
    Introduction: Taxus species are used as medicinal plants all over the world. The leaves of Taxus species are sustainable medicinal resources that are rich in taxoids and flavonoids. However, traditional identification methods cannot effectively identify Taxus species on the basis of leaces used as raw medicinal materials, because their appearance and morphological characteristics are almost the same, and the probability of error identification increases in accordance with the subjective consciousness of the experimenter. Moreover, although the leaves of different Taxus species have been widely used, their chemical components are similar and lack systematic comparative research. Such a situation is challenging for quality assessment. Materials and methods: In this study, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry combined with chemometrics was applied for the simultaneous determination of eight taxoids, four flavanols, five flavonols, two dihydroflavones, and five biflavones in the leaves of six Taxus species, namely, T. mairei, T. chinensis, T. yunnanensis, T. wallichiana, T. cuspidata, and T. media. Chemometric methods, including hierarchical cluster analysis, principal component analysis, orthogonal partial least squares-discriminate analysis, random forest iterative modeling, and fisher linear discriminant analysis, were utilized to differentiate and evaluate the six Taxus species. Results: This proposed method exhibited good linearity (R 2 = 0.9999-0.9972) with a lower quantification limits of 0.94-3.05 ng/mL for all analytes. The intra- and inter-day precisions were within 6.83%. Six compounds, namely, 7-xylosyl-10-deacetyltaxol, ginkgetin, rutin, aromadendrin, 10-deacetyl baccatin III, and epigallocatechin, were identified through chemometrics for the first time. These compounds can be used as important chemical markers to distinguish the above six Taxus species rapidly. Conclusion: This study established a method for determination of the leaves of six Taxus species, and revealing the differences in the chemical components of these six Taxus species.
  5. Therapeutic evaluation and metabolic reprograming of isosteviol sodium in a rat model of ischemic cardiomyopathy
    Cao Y, Lu Z, Wang D, Tan KS, Liu W, Wu Q, et al.
    Eur J Pharmacol, 2021 Nov 15;911:174539.
    PMID: 34599913 DOI: 10.1016/j.ejphar.2021.174539
    Ischemia heart disease, one of the lethal cardiovascular diseases, irreversibly impairs cardiac function and is recognized as the primary risk factor for mortality in industrialized countries. The myocardial ischemia treatment still faces a considerable degree of increasing unmet needs. Isosteviol sodium (STVNa) and its derivatives have been proven to effectively alleviate metabolic diseases, hypertension, and heart hypertrophy. Little is known about how STVNa confers the cardioprotective effect during acute myocardial ischemia (AMI). In the present study, a rat model of acute ST-segment-elevation myocardial ischemia by left anterior descending (LAD) ligation was established. Compared to the AMI model group, STVNa administration (4 mg/kg, twice a day) well preserved left ventricle function by ejection fraction (45.10 ± 10.39 vs. 73.64 ± 13.15, p = 0.0013) and fractional shortening (22.94 ± 6.28 vs. 44.00 ± 11.05, p = 0.0017). Further analysis shows that high-dose STVNa (4 mg/kg) significantly improved the hemodynamics in AMI rats, with LVSP (88.25 ± 12.78 vs 99.75 ± 5.10, p = 0.018), max dP/dt (2978.45 ± 832.46 vs 4048.56 ± 827.23, p = 0.096), LVEDP (19.88 ± 2.00 vs 22.26 ± 3.21, p = 0.04) and left ventricular relaxation time constant (Tau) (0.030 ± 0.006 vs 0.021 ± 0.004, p = 0.021). Mechanically, STVNa administration retained the myocardial levels of phosphorylated AMPK, and CPT1b. Moreover, STVNa significantly increased the total energy expenditure, and reduced fatty acid accumulation through mitochondrial oxidative phosphorylation, which was supported by the indirect calorimetry and cellular energy analysis. Taken together, these findings suggest that STVNa is a potential cardioprotection agent for ischemic cardiomyopathy, likely through improving energy homeostasis, left ventricular hemodynamics, and heart function.
  6. Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity
    Chen M, Samuel VP, Wu Y, Dang M, Lin Y, Sriramaneni R, et al.
    J Environ Pathol Toxicol Oncol, 2019;38(2):143-152.
    PMID: 31679277 DOI: 10.1615/JEnvironPatholToxicolOncol.2019029341
    The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.
  7. The Attenuation of Chronic Ulcerative Colitis by (R)-salbutamol in Repeated DSS-Induced Mice
    Deng L, Guo H, Wang S, Liu X, Lin Y, Zhang R, et al.
    Oxid Med Cell Longev, 2022;2022:9318721.
    PMID: 35178163 DOI: 10.1155/2022/9318721
    Racemic salbutamol ((RS)-sal), which consist of the same amount of (R)-sal and (S)-sal, has been used for asthma and COPD due to its bronchodilation effect. However, the effect of (R)-sal on repeated dextran sulfate sodium (DSS)-induced chronic colitis has not yet been investigated. In this study evaluated the potential effect of (R)-, (S)-, and (RS)-sal in mice with repeated DSS-induced chronic colitis and investigated the underlying mechanisms. Here, we verified that chronic colitis was significantly attenuated by (R)-sal, which was evidenced by notably mitigated body weight loss, disease activity index (DAI), splenomegaly, colonic lengths shortening, and histopathological scores. (R)-sal treatment noticeably diminished the levels of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, and IFN-γ). Notably, the efficacy of (R)-sal was better than that of (RS)-sal. Further research revealed that (R)-sal mitigated colonic CD4 leukocyte infiltration, decreased NF-κB signaling pathway activation, improved the Nrf-2/HO-1 signaling pathway, and increased the expression of ZO-1 and occludin. In addition, (R)-sal suppressed the levels of TGF-β1, α-SMA, and collagen in mice with chronic colitis. Furthermore, the 16S rDNA sequences analyzed of the intestinal microbiome revealed that (R)-sal could mitigate the intestinal microbiome structure and made it more similar to the control group, which mainly by relieving the relative abundance of pathogens (such as Bacteroides) and increasing the relative abundance of probiotics (such as Akkermansia). Therefore, (R)-sal ameliorates repeated DSS-induced chronic colitis in mice by improving inflammation, suppressing oxidative stress, mitigating intestinal barrier function, relieving intestinal fibrosis, and regulating the intestinal microbiome community. These results indicate that (R)-sal maybe a novel treatment alternative for chronic colitis.
  8. (RS)-bambuterol and its enantiomers: Potential improvement of (R)-bambuterol in mice with colitis
    Deng L, Wang S, Guo H, Liu X, Zou X, Zhang R, et al.
    Int Immunopharmacol, 2022 Feb;103:108501.
    PMID: 34974400 DOI: 10.1016/j.intimp.2021.108501
    Bambuterol (BMB) has been used clinically to treat asthma due to its bronchodilation activity. However, the effect of BMB on ulcerative colitis (UC) has not been examined. The present work focused on the effects of enantiomeric BMB on UC. Acute UC was induced in mice by 3% dextran sulfate sodium (DSS), and (R)-, (S) and (RS)-BMB were orally administered. Body weight loss and the disease activity index (DAI) were measured once a day. Inflammatory factors were detected by ELISA and qRT-PCR. Histological evaluations of colon samples were performed. IL-6, STAT3, and RORγt pathway-related proteins were analyzed by western blotting. The results verified that colitis severity was dramatically ameliorated by (R)-BMB, which was significantlybetter than the effect of (RS)-BMB or (S)-BMB, as evidenced by body weight loss, DAI, colon length, spleen/body weight ratio and histopathological manifestations. Furthermore, (R)-BMB treatment significantly diminished the levels of inflammatory cytokines and macrophages infiltration in mice with colitis. Besides, treated with (R)-BMB obviously elevated the level of β2AR. In addition, (R)-BMB decreased the expression of IL-6, IL-17, retinoic acid receptor-related orphan receptor-gamma t (RORt), and phosphorylated STAT3 (p-STAT3) in a dose-dependent manner in the colon tissues. The efficacy of (R)-BMB was more notable than aminosalicylic acid (5-ASA). (R)-BMB is either butyrilcholinesterase inhibitor or β2AR agonist which offers new treatment of colitis.
  9. Fulltext In COVID-19 Health Messaging, Loss Framing Increases Anxiety with Little-to-No Concomitant Benefits: Experimental Evidence from 84 Countries
    Dorison CA, Lerner JS, Heller BH, Rothman AJ, Kawachi II, Wang K, et al.
    Affect Sci, 2022 Sep;3(3):577-602.
    PMID: 36185503 DOI: 10.1007/s42761-022-00128-3
    The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
  10. Temporal population variability in local forest communities has mixed effects on tree species richness across a latitudinal gradient
    Fung T, Chisholm RA, Anderson-Teixeira K, Bourg N, Brockelman WY, Bunyavejchewin S, et al.
    Ecol Lett, 2020 Jan;23(1):160-171.
    PMID: 31698546 DOI: 10.1111/ele.13412
    Among the local processes that determine species diversity in ecological communities, fluctuation-dependent mechanisms that are mediated by temporal variability in the abundances of species populations have received significant attention. Higher temporal variability in the abundances of species populations can increase the strength of temporal niche partitioning but can also increase the risk of species extinctions, such that the net effect on species coexistence is not clear. We quantified this temporal population variability for tree species in 21 large forest plots and found much greater variability for higher latitude plots with fewer tree species. A fitted mechanistic model showed that among the forest plots, the net effect of temporal population variability on tree species coexistence was usually negative, but sometimes positive or negligible. Therefore, our results suggest that temporal variability in the abundances of species populations has no clear negative or positive contribution to the latitudinal gradient in tree species richness.
  11. Production of medium-chain fatty acid caproate from Chinese liquor distillers' grain using pit mud as the fermentation microbes
    Gao M, Lin Y, Wang P, Jin Y, Wang Q, Ma H, et al.
    J Hazard Mater, 2021 Sep 05;417:126037.
    PMID: 33992013 DOI: 10.1016/j.jhazmat.2021.126037
    Chinese liquor distillers' grain (CLDG) is an abundant industrial organic waste showing high potential as feedstock for biofuel conversion. In this study, CLDG was used as substrate by microbial community in pit mud to produce medium-chain fatty acids (especially caproate). Simulated and real fermentation were used to evaluate the effect of ethanol and lactic acid being the electronic donors (EDs) during the anaerobic chain elongation (CE). The caproate concentration was achieved at 449 mg COD/g VS, with the corresponding high carbon selectivity at 37.1%. Microbial analysis revealed that the domestication of pit mud increased the abundance of Caproiciproducens (converting lactic acid into caproate) and Lactobacillus (producing lactic acid), leading to enhanced caproate production. The lactic acid conversion facilitated in full utilization of ethanol through CE consumption. The coexistence of EDs benefited the CE system and that this green energy production can be a promising high-performance biofuel donor for sustainable industrial production development.
  12. Photodynamic inactivation of Burkholderia cepacia by curcumin in combination with EDTA
    Hu J, Lin S, Tan BK, Hamzah SS, Lin Y, Kong Z, et al.
    Food Res Int, 2018 09;111:265-271.
    PMID: 30007685 DOI: 10.1016/j.foodres.2018.05.042
    Burkholderia cepacia (B. cepacia) is an aerobic Gram-negative bacillus found in various aquatic environments and can cause food contamination. We investigated the photodynamic antibacterial effects of food additive curcumin combined with EDTA on B. cepacia. We found a ~4-log reduction in B. cepacia viability when photo-irradiated with curcumin at 50 μM by blue LED light (16 mW/cm2) for 30 min with 0.4% (w/v) EDTA. Moreover, the bacterial morphological alterations and the leakage of intracellular contents were observed after photodynamic treatment. There were also obvious genomic DNA cleavage and a general loss of bacterial proteins assigned to large-scale protein degradation after photodynamic inactivation treatment. Collectively, curcumin in combination with EDTA illuminated by blue LED is a potential candidate for photodynamic inactivation of B. cepacia.
  13. Fulltext Determinants of gastric cancer screening attendance in Southeastern China: a cross-sectional study
    Huang Z, Hu Z, Wong LP, Lin Y
    BMJ Open, 2023 Jul 20;13(7):e073925.
    PMID: 37474189 DOI: 10.1136/bmjopen-2023-073925
    OBJECTIVES: This study aimed to identify the determinants of gastric cancer screening attendance among individuals aged 40 years in a region with high gastric cancer in China.

    DESIGN: An anonymous, cross-sectional survey was conducted between October 2021 and March 2022.

    SETTING: A self-administered online survey was conducted in Fujian Province in Southeastern China.

    PARTICIPANTS: People aged 40 years living in five selected cities in Fujian Province with no history of cancer.

    MAIN OUTCOME MEASURES: Gastric cancer screening attendance was measured with the question 'Have you ever been screened for gastric cancer in the past'.

    RESULTS: In total, 2547 complete responses were obtained. The mean age of respondents was 47.72±7.20 years, and 59.8% were men. A total of 42.6% of participants reported that they had undergone gastric cancer screening. The result of multivariable logistic regression analysis showed that participants with a first-degree relative affected with gastric cancer (OR=2.02, 95% CI: 1.58 to 2.59) and high perceived susceptibility of gastric cancer (OR=2.03, 95% CI: 1.58 to 2.59) were the strongest facilitators for screening attendance. Other factors positively associated with screening attendance were age 51-60 years (OR=1.69, 95% CI: 1.31 to 2.18), living in urban regions (OR=1.27, 95% CI: 1.05 to 1.55), friends/neighbours/colleagues with gastric cancer (OR=1.30, 95% CI: 1.07 to 1.58), history of chronic gastric disease (OR=1.90, 95% CI: 1.57 to 2.30), perceived high cost (OR=1.28, 95% CI: 1.01 to 1.61) and physician recommendation (OR=1.71, 95% CI: 1.36 to 2.16). On the other hand, factors negatively associated with screening attendance included perceived barriers, namely screening is only necessary when symptoms present (OR=0.71, 95% CI: 0.58 to 0.87) and perceived appointment for gastroscopy screening is difficult and time-consuming (OR=0.75, 95% CI: 0.60 to 0.94). No significant association was found between knowledge level and participation in screening.

    CONCLUSION: This study highlights important individual-level factors and barriers to gastric cancer screening. Strategies targeting under-screened populations and eliminating patient-perceived barriers to gastric cancer screening are essential.

  14. Identification of chronic obstructive pulmonary disease subgroups in 13 Asian cities
    Kim WJ, Gupta V, Nishimura M, Makita H, Idolor L, Roa C, et al.
    Int J Tuberc Lung Dis, 2018 07 01;22(7):820-826.
    PMID: 29914609 DOI: 10.5588/ijtld.17.0524
    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment.

    OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup.

    METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis.

    RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score.

    CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

  15. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
    Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  16. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
    Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  17. Fulltext Genetic and clinical characteristics of Chinese children with Glucokinase-maturity-onset diabetes of the young (GCK-MODY)
    Li X, Ting TH, Sheng H, Liang CL, Shao Y, Jiang M, et al.
    BMC Pediatr, 2018 03 06;18(1):101.
    PMID: 29510678 DOI: 10.1186/s12887-018-1060-8
    BACKGROUND: There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY.

    METHODS: Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children's hospital in South China. Clinical data were obtained from medical records. Blood was collected from the patients and their parents for glucokinase (GCK) gene analysis. Parents without diabetes were tested for fasting glucose and HbA1c. Clinical information and blood for GCK gene analysis were obtained from grandparents with diabetes. GCK gene mutational analysis was performed by polymerase chain reaction and direct sequencing. Patients without a GCK gene mutation were screened by targeted next-generation sequencing (NGS) technology for other MODY genes.

    RESULTS: Nine children tested positive for GCK gene mutations while two were negative. The nine GCK-MODY patients were from unrelated families, aged 1 month to 9 years and 1 month at first detection of hyperglycaemia. Fasting glucose was elevated (6.1-8.5 mmol/L), HbA1c 5.2-6.7% (33.3-49.7 mmol/mol), both remained stable on follow-up over 9 months to 5 years. Five detected mutations had been previously reported: p.Val182Met, c.679 + 1G > A, p.Gly295Ser, p.Arg191Gln and p.Met41Thr. Four mutations were novel: c.483 + 2 T > A, p.Ser151del, p.Met57GlyfsX29 and p.Val374_Ala377del. No mutations were identified in the other two patients, who were also tested by NGS.

    CONCLUSIONS: GCK gene mutations are detected in Chinese children and their family members with typical clinical features of GCK-MODY. Four novel mutations are detected.
  18. Fulltext A review of Crassignatha (Araneae, Symphytognathidae)
    Li Y, Lin Y, Li S
    Zookeys, 2020;988:63-128.
    PMID: 33223891 DOI: 10.3897/zookeys.988.56188
    Crassignatha Wunderlich, 1995 is redefined to include species with six eyes in three diads, chelicerae fused only near the base, sculpturing on the carapace, one or two clasping spurs on tibia II, a bilateral scutum of the male abdomen, and globular spermathecae and adjacent copulatory openings in the female. A key and distribution map are provided for 24 Crassignatha species in this paper. Diagnoses and illustrated photographs are provided for 22 species from China, Malaysia, Thailand, and Vietnam. Thirteen species are described and documented as new to science: C. baihua Y. Lin & S. Li, sp. nov. (♂♀), C. bangbie Y. Lin & S. Li, sp. nov. (♀), C. changyan Y. Lin & S. Li, sp. nov. (♀), C. dongnai Y. Lin & S. Li, sp. nov. (♀), C. gucheng Y. Lin & S. Li, sp. nov. (♂♀), C. mengla Y. Lin & S. Li, sp. nov. (♂♀), C. nantou Y. Lin & S. Li, sp. nov. (♂♀), C. nasalis Y. Lin & S. Li, sp. nov. (♂♀), C. rostriformis Y. Lin & S. Li, sp. nov. (♂♀), C. shunani Y. Lin & S. Li, sp. nov. (♂♀), C. si Y. Lin & S. Li, sp. nov. (♂♀), C. thamphra Y. Lin & S. Li, sp. nov. (♀), and C. xichou Y. Lin & S. Li, sp. nov. (♀). Three new combinations are proposed: C. bicorniventris (Lin & Li, 2009), comb. nov., C. quadriventris (Lin & Li, 2009), comb. nov., and C. shiluensis (Lin & Li, 2009), comb. nov. are transferred from Patu Marples, 1951. DNA barcodes and genetic distances of seventeen species are obtained to confirm correct identification. Types of seven known Chinese Crassignatha species are re-examined, and the taxonomic placement of C. longtou Miller, Griswold & Yin, 2009 may be incorrect based on morphological and molecular data.
  19. Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats
    Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X
    Drug Dev Res, 2019 09;80(6):837-845.
    PMID: 31301179 DOI: 10.1002/ddr.21567
    The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.
  20. Fulltext A common variant near TGFBR3 is associated with primary open angle glaucoma
    Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, et al.
    Hum Mol Genet, 2015 Jul 01;24(13):3880-92.
    PMID: 25861811 DOI: 10.1093/hmg/ddv128
    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
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