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  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.
  2. 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
  3. Jama HA, Muralitharan RR, Xu C, O'Donnell JA, Bertagnolli M, Broughton BRS, et al.
    Br J Pharmacol, 2022 Mar;179(5):918-937.
    PMID: 34363610 DOI: 10.1111/bph.15650
    Elevated blood pressure (BP), or hypertension, is the main risk factor for cardiovascular disease. As a multifactorial and systemic disease that involves multiple organs and systems, hypertension remains a challenging disease to study. Models of hypertension are invaluable to support the discovery of the specific genetic, cellular and molecular mechanisms underlying essential hypertension, as well as to test new possible treatments to lower BP. Rodent models have proven to be an invaluable tool for advancing the field. In this review, we discuss the strengths and weaknesses of rodent models of hypertension through a systems approach. We highlight the ways how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), immune system and the gut microbiota influence BP in each rodent model. We also discuss often overlooked hypertensive conditions such as pulmonary hypertension and hypertensive-pregnancy disorders, providing an important resource for researchers. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.
  4. Ren T, Feng H, Xu C, Xu Q, Fu B, Azwar E, et al.
    Chemosphere, 2022 Jan 22;294:133710.
    PMID: 35074326 DOI: 10.1016/j.chemosphere.2022.133710
    The usage of fertilizer with high nitrogen content in many countries, as well as its enormous surplus, has a negative impact on the soil ecological environment in agricultural system. This consumption of nitrogen fertilizer can be minimized by applying biochar to maintain the sufficient supply of nitrogen as nutrient to the near-root zone. This study investigated the effects of various amounts of biochar application (450, 900, 1350, and 1800 kg/hm2) and reduction of nitrogen fertilizer amount (10, 15, 20, and 25%) on the nutrients and microorganism community structure in rhizosphere growing tobacco plant. The microorganism community was found essential in improving nitrogen retention. Compared with conventional treatment, an application of biochar in rhizosphere soil increased the content of soil available phosphorus, organic matter and total nitrogen by 21.47%, 26.34%, and 9.52%, respectively. It also increased the abundance of microorganisms that are capable of degrading and utilizing organic matter and cellulose, such as Actinobacteria and Acidobacteria. The relative abundance of Chloroflexi was also increased by 49.67-78.61%, and the Acidobacteria increased by 14.79-39.13%. Overall, the application of biochar with reduced nitrogen fertilizer amount can regulate the rhizosphere microecological environment of tobacco plants and their microbial population structure, thereby promoting soil health for tobacco plant growth while reducing soil acidification and environmental pollution caused by excessive nitrogen fertilizer.
  5. Ren T, Chen N, Wan Mahari WA, Xu C, Feng H, Ji X, et al.
    Environ Res, 2021 01;192:110273.
    PMID: 33002505 DOI: 10.1016/j.envres.2020.110273
    Pot experiments were conducted to investigate the influence of biochar addition and the mechanisms that alleviate Cd stress in the growth of tobacco plant. Cadmium showed an inhibitory effect on tobacco growth at different post-transplantation times, and this increased with the increase in soil Cd concentration. The growth index decreased by more than 10%, and the photosynthetic pigment and photosynthetic characteristics of the tobacco leaf were significantly reduced, and the antioxidant enzyme activity was enhanced. Application of biochar effectively alleviated the inhibitory effect of Cd on tobacco growth, and the alleviation effect of treatments is more significant to the plants with a higher Cd concentration. The contents of chlorophyll a, chlorophyll b, and carotenoids in the leaves of tobacco plants treated with biochar increased by 9.99%, 12.58%, and 10.32%, respectively, after 60 days of transplantation. The photosynthetic characteristics index of the net photosynthetic rate increased by 11.48%, stomatal conductance increased by 11.44%, and intercellular carbon dioxide concentration decreased to 0.92. Based on the treatments, during the growth period, the antioxidant enzyme activities of tobacco leaves comprising catalase, peroxidase, superoxide dismutase, and malondialdehyde increased by 7.62%, 10.41%, 10.58%, and 12.57%, respectively, after the application of biochar. Our results show that biochar containing functional groups can effectively reduce the effect of Cd stress by intensifying the adsorption or passivation of Cd in the soil, thereby, significantly reducing the Cd content in plant leaves, and providing a theoretical basis and method to alleviate soil Cd pollution and effect soil remediation.
  6. Cai W, Xu C, Yu S, Gong X
    Front Psychol, 2022;13:745259.
    PMID: 35478733 DOI: 10.3389/fpsyg.2022.745259
    Based on the transaction theory of stress and the theory of resource conservation, which introduces knowledge acquisition and intrinsic motivation as mediating variables, a chain mediating model for the influence of challenge-hindrance stress on innovation performance is constructed. Data of 295 samples collected in three stages were used to testify hypothesis. The results confirmed a positive relationship between challenge stress and innovation performance, and a negative relationship between hindrance stress and innovation performance. Intrinsic motivation and knowledge acquisition play a parallel and chain mediating role in the relationship between challenge-hindrance stress and innovation performance. These findings contribute to a deeper understanding of how challenge -hindrance stress affects innovation performance and provide important practical guidance for improving innovation performance.
  7. Luo Y, Xia J, Zhao Z, Chang Y, Bee YM, Nguyen KT, et al.
    J Diabetes, 2023 Apr 10.
    PMID: 37038616 DOI: 10.1111/1753-0407.13381
    AIMS: To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin-naïve patients with type 2 diabetes mellitus.

    METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO.

    RESULTS: Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta-analyses and network meta-analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U-300 or degludec U-100, glargine U-100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U-100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin 

  8. Ji L, Luo Y, Bee YM, Xia J, Nguyen KT, Zhao W, et al.
    J Diabetes, 2023 Jun;15(6):474-487.
    PMID: 37088916 DOI: 10.1111/1753-0407.13392
    The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins (glargine U-300, degludec U-100, glargine U-100, detemir, and insulin protamine Hagedorn) in insulin-naïve adult patients with type 2 diabetes in the Asia-Pacific region. Based on evidence from a systematic review, we developed an Asia-Pacific clinical practice guideline through comprehensive internal review and external review processes. We set up and used clinical thresholds of trivial, small, moderate, and large effects for different critical and important outcomes in the overall certainty of evidence assessment and balancing the magnitude of intervention effects when making recommendations, following GRADE methods (Grading of Recommendations, Assessment, Development, and Evaluation). The AGREE (Appraisal of Guidelines, Research and Evaluation) and RIGHT (Reporting Items for practice Guidelines in HealThcare) guideline reporting checklists were complied with. After the second-round vote by the working group members, all the recommendations and qualifying statements reached over 75% agreement rates. Among 44 contacted external reviewers, we received 33 clinicians' and one patient's comments. The overall response rate was 77%. To solve the four research questions, we made two strong recommendations, six conditional recommendations, and two qualifying statements. Although the intended users of this guideline focused on clinicians in the Asia-Pacific region, the eligible evidence was based on recent English publications. We believe that the recommendations and the clinical thresholds set up in the guideline can be references for clinicians who take care of patients with type 2 diabetes worldwide.
  9. Liu X, Zhang R, Shi H, Li X, Li Y, Taha A, et al.
    Mol Med Rep, 2018 05;17(5):7227-7237.
    PMID: 29568864 DOI: 10.3892/mmr.2018.8791
    Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA‑induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose‑regulated protein 78, C/EBP‑homologous protein, nuclear factor‑κB and cleaved caspase‑3, while upregulating the expression of Bcl‑2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)‑1 and MMP‑3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor‑β (TGF‑β) and Smad2/3, and decreasing the expression of the TGF‑β inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA‑induced photoaging and highlight the potential for the application of Cur in skin photoprotection.
  10. Johnson DJ, Needham J, Xu C, Massoud EC, Davies SJ, Anderson-Teixeira KJ, et al.
    Nat Ecol Evol, 2018 09;2(9):1436-1442.
    PMID: 30104751 DOI: 10.1038/s41559-018-0626-z
    Survival rates of large trees determine forest biomass dynamics. Survival rates of small trees have been linked to mechanisms that maintain biodiversity across tropical forests. How species survival rates change with size offers insight into the links between biodiversity and ecosystem function across tropical forests. We tested patterns of size-dependent tree survival across the tropics using data from 1,781 species and over 2 million individuals to assess whether tropical forests can be characterized by size-dependent life-history survival strategies. We found that species were classifiable into four 'survival modes' that explain life-history variation that shapes carbon cycling and the relative abundance within forests. Frequently collected functional traits, such as wood density, leaf mass per area and seed mass, were not generally predictive of the survival modes of species. Mean annual temperature and cumulative water deficit predicted the proportion of biomass of survival modes, indicating important links between evolutionary strategies, climate and carbon cycling. The application of survival modes in demographic simulations predicted biomass change across forest sites. Our results reveal globally identifiable size-dependent survival strategies that differ across diverse systems in a consistent way. The abundance of survival modes and interaction with climate ultimately determine forest structure, carbon storage in biomass and future forest trajectories.
  11. Luo Y, Chang Y, Zhao Z, Xia J, Xu C, Bee YM, et al.
    Lancet Reg Health West Pac, 2023 Jun;35:100746.
    PMID: 37424694 DOI: 10.1016/j.lanwpc.2023.100746
    BACKGROUND: Technological advances make it possible to use device-supported, automated algorithms to aid basal insulin (BI) dosing titration in patients with type 2 diabetes.

    METHODS: A systematic review and meta-analysis of randomized controlled trials were performed to evaluate the efficacy, safety, and quality of life of automated BI titration versus conventional care. The literature in Medline, Embase, Web of Science, and the Cochrane databases from January 2000 to February 2022 were searched to identify relevant studies. Risk ratios (RRs), mean differences (MDs), and their 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

    FINDINGS: Six of the 7 eligible studies (889 patients) were included in meta-analyses. Low- to moderate-quality evidence suggests that patients who use automated BI titration versus conventional care may have a higher probability of reaching a target of HbA1c <7.0% (RR, 1.82 [95% CI, 1.16-2.86]); and a lower level of HbA1c (MD, -0.25% [95% CI, -0.43 to -0.06%]). No statistically significant differences were detected between the two groups in fasting glucose results, incidences of hypoglycemia, severe or nocturnal hypoglycemia, and quality of life, with low to very low certainty for all the evidence.

    INTERPRETATION: Automated BI titration is associated with small benefits in reducing HbA1c without increasing the risk of hypoglycemia. Future studies should explore patient attitudes and the cost-effectiveness of this approach.

    FUNDING: Sponsored by the Chinese Geriatric Endocrine Society.

  12. Lin GW, Xu C, Chen K, Huang HQ, Chen J, Song B, et al.
    Lancet Oncol, 2020 02;21(2):306-316.
    PMID: 31879220 DOI: 10.1016/S1470-2045(19)30799-5
    BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL.

    METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.

    FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.

    INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.

    FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.

  13. McDowell N, Allen CD, Anderson-Teixeira K, Brando P, Brienen R, Chambers J, et al.
    New Phytol, 2018 08;219(3):851-869.
    PMID: 29451313 DOI: 10.1111/nph.15027
    Tree mortality rates appear to be increasing in moist tropical forests (MTFs) with significant carbon cycle consequences. Here, we review the state of knowledge regarding MTF tree mortality, create a conceptual framework with testable hypotheses regarding the drivers, mechanisms and interactions that may underlie increasing MTF mortality rates, and identify the next steps for improved understanding and reduced prediction. Increasing mortality rates are associated with rising temperature and vapor pressure deficit, liana abundance, drought, wind events, fire and, possibly, CO2 fertilization-induced increases in stand thinning or acceleration of trees reaching larger, more vulnerable heights. The majority of these mortality drivers may kill trees in part through carbon starvation and hydraulic failure. The relative importance of each driver is unknown. High species diversity may buffer MTFs against large-scale mortality events, but recent and expected trends in mortality drivers give reason for concern regarding increasing mortality within MTFs. Models of tropical tree mortality are advancing the representation of hydraulics, carbon and demography, but require more empirical knowledge regarding the most common drivers and their subsequent mechanisms. We outline critical datasets and model developments required to test hypotheses regarding the underlying causes of increasing MTF mortality rates, and improve prediction of future mortality under climate change.
  14. Yan S, Ren T, Wan Mahari WA, Feng H, Xu C, Yun F, et al.
    Sci Total Environ, 2021 Aug 24;802:149835.
    PMID: 34461468 DOI: 10.1016/j.scitotenv.2021.149835
    Soil carbon supplementation is known to stimulate plant growth by improving soil fertility and plant nutrient uptake. However, the underlying process and chemical mechanism that could explain the interrelationship between soil carbon supplementation, soil micro-ecology, and the growth and quality of plant remain unclear. In this study, we investigated the influence and mechanism of soil carbon supplementation on the bacterial community, chemical cycling, mineral nutrition absorption, growth and properties of tobacco leaves. The soil carbon supplementation increased amino acid, carbohydrates, chemical energy metabolism, and bacterial richness in the soil. This led to increased content of sugar (23.75%), starch (13.25%), and chlorophyll (10.56%) in tobacco leaves. Linear discriminant analysis revealed 49 key phylotypes and significant increment of some of the Plant Growth-Promoting Rhizobacteria (PGPR) genera (Bacillus, Novosphingobium, Pseudomonas, Sphingomonas) in the rhizosphere, which can influence the tobacco growth. Partial Least Squares Path Modeling (PLS-PM) showed that soil carbon supplementation positively affected the sugar and starch contents in tobacco leaves by possibly altering the photosynthesis pathway towards increasing the aroma of the leaves, thus contributing to enhanced tobacco flavor. These findings are useful for understanding the influence of soil carbon supplementation on bacterial community for improving the yields and quality of tobacco in industrial plantation.
  15. Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, et al.
    Trends Parasitol, 2021 01;37(1):8-11.
    PMID: 33153922 DOI: 10.1016/j.pt.2020.10.003
    Artemisinin-based combination therapies (ACTs) have demonstrated in vitro inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Artemisinins have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe coronavirus disease 2019 (COVID-19). There is now sufficient evidence for the effectiveness of ACTs, and in particular artesunate/pyronaridine, to support clinical studies for COVID-19 infections.
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