Displaying publications 21 - 40 of 42 in total

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  1. Zhou J, Lam B, Neogi S, Yeo G, Azizan E, Brown M
    J Hypertens, 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e40.
    PMID: 27753883
    Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.
  2. 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.
  3. Asteris PG, Gandomi AH, Armaghani DJ, Tsoukalas MZ, Gavriilaki E, Gerber G, et al.
    J Cell Mol Med, 2024 Feb;28(4):e18105.
    PMID: 38339761 DOI: 10.1111/jcmm.18105
    Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs. non-ICU admission). A recently introduced alpha-index identified the 30 most predictive genetic variants. DERGA algorithm, which employs multiple classification algorithms, determined the optimal pattern of these key variants, resulting in 97% accuracy for predicting disease outcome. Individual variations ranged from 40 to 161 variants per patient, with 977 total variants detected. This study demonstrates the utility of alpha-index in ranking a substantial number of genetic variants. This approach enables the implementation of well-established classification algorithms that effectively determine the relevance of genetic variants in predicting outcomes with high accuracy.
  4. Zhou JN, Lin BR, Shen HF, Pu XM, Chen ZN, Feng JJ
    Plant Dis, 2012 May;96(5):760.
    PMID: 30727539 DOI: 10.1094/PDIS-11-11-0942
    Phalaenopsis orchids, originally from tropical Asia, are mainly planted in Thailand, Singapore, Malaysia, the Philippines, and Taiwan and have gained popularity from consumers all over the world. The cultivation area of Phalaenopsis orchids has been rising and large-scale bases have been established in mainland China, especially South China because of suitable environmental conditions. In September 2011, a soft rot of Phalaenopsis aphrodita was found in a Phalaenopsis planting base in Guangzhou with an incidence of ~15%. Infected plants initially showed water-soaked, pale-to-dark brown pinpoint spots on leaves that were sometimes surrounded by a yellow halo. Spots expanded rapidly with rising humidity and temperatures, and in a few days, severely extended over the blade with a light tan color and darker brown border. Lesions decayed with odorous fumes and tissues collapsed with inclusions exuding. The bacterium advanced to the stem and pedicle. Finally, leaves became papery dry and the pedicles lodged. Six diseased samples were collected, and bacteria were isolated from the edge of symptomatic tissues after sterilization in 0.3% NaOCl for 10 min, rinsing in sterile water three times, and placing on nutrient agar for culture. Twelve representative isolates were selected for further characterization. All strains were gram negative, grew at 37°C, were positive for indole production, and utilized malonate, glucose, and sucrose but not glucopyranoside, trehalose, or palatinose. Biolog identification (version 4.20.05, Hayward, CA) was performed and Pectobacterium chrysanthemi (SIM 0.868) was confirmed for the tested isolates (transfer to genus Dickeya). PCR was used to amplify the 16S rDNAgene with primers 27f and 1492r, dnaX gene with primers dnaXf and dnaXr (3), and gyrB gene with primers gyrBf (5'-GAAGGYAAAVTKCATCGTCAGG-3') and gyrB-r1 (5'-TCARATATCRATATTCGCYGCTTTC-3') designed on the basis of the published gyrB gene sequences of genus Dickeya. BLASTn was performed online, and phylogeny trees (100% bootstrap values) were created by means of MEGA 5.05 for these gene sequences, respectively. Results commonly showed that the representative tested strain, PA1, was most homologous to Dickeya dieffenbachiae with 98% identity for 16S rDNA(JN940859), 97% for dnaX (JN989971), and 96% for gyrB (JN971031). Thus, we recommend calling this isolate D. dieffenbachiae PA1. Pathogenicity tests were conducted by injecting 10 P. aphrodita seedlings with 100 μl of the bacterial suspension (1 × 108 CFU/ml) and another 10 were injected with 100 μl of sterile water as controls. Plants were inoculated in a greenhouse at 28 to 32°C and 90% relative humidity. Soft rot symptoms were observed after 2 days on the inoculated plants, but not on the control ones. The bacterium was isolated from the lesions and demonstrated identity to the inoculated plant by the 16S rDNA sequence comparison. Previously, similar diseases of P. amabilis were reported in Tangshan, Jiangsu, Zhejiang, and Wuhan and causal agents were identified as Erwinia spp. (2), Pseudomonas grimontii (1), E. chrysanthemi, and E. carotovora subsp. carovora (4). To our knowledge, this is the first report of D. dieffenbachiae causing soft rot disease on P. aphrodita in China. References: (1) X. L. Chu and B. Yang. Acta Phytopathol. Sin. 40:90, 2010. (2) Y. M. Li et al. J. Beijing Agric. Coll. 19:41, 2004. (3) M. Sławiak et al. Eur. J. Plant Pathol. 125:245, 2009. (4) Z. Y. Wu et al. J. Zhejiang For. Coll. 27:635, 2010.
  5. Zhou JN, Liu SY, Chen YF, Liao LS
    Plant Dis, 2015 Mar;99(3):416.
    PMID: 30699721 DOI: 10.1094/PDIS-10-14-1025-PDN
    Clausena lansium, also known as wampee (Clausena wampi), is a plant species native to China, Vietnam, the Philippines, Malaysia, and Indonesia, where it is widely cultivated, and also grown in India, Sri Lanka, Queensland, Florida, and Hawaii, but less frequently (3). The fruit can be consumed fresh or made into juice, jam, or succade. In summer to fall 2014, a soft rot disease was found in a wampee planting region in Yunan County, Guangdong Province, China. On Sept. 18, we collected diseased samples from a wampee orchard with about 20% disease incidence. The infected fruit initially showed pinpoint spots on the peel, water-soaked lesions, and light to dark brown discoloration. Spots expanded in 2 days, and tissues collapsed after 5 days. Severely affected fruit showed cracking or nonodorous decay. Five diseased samples were collected, and causal agents were isolated from symptomatic tissues 1 cm under the peel after surface sterilization in 0.3% NaOCl for 10 min and rinsing in sterile water three times. Tissues were placed on a Luria Bertani (LB) plate for culture. Ten representative isolates were selected for further characterization. No colony was isolated from healthy tissues. Colonies were round, smooth, with irregular edges, and produced a yellow pigment in culture. Biolog identification (Version 4.20.05) showed that all strains were gram negative, negative for indole production, and utilized glucose, maltose, trehalose, sucrose, D-lactose, and pectin but not sorbitol or gelatin. The isolates were identified as Pantoea agglomerans (SIM 0.69). Multilocus sequence analysis (MLSA) was conducted for rapid classification of the strains. Sequences of atpD, gyrB, infB, and rpoB were amplified using corresponding primers (2). All sequences of the 10 isolates were identical in each gene. BLASTn was performed, and maximum likelihood trees based on the concatenated nucleotide sequences of the four genes were constructed using MEGA6. Bootstrap values after 1,000 replicates were expressed as percentages. Results showed that the tested strain named CL1 was most homologous to P. anthophila, with 98% identity for atpD (KM521543), 100% for gyrB (KM521544), infB (KM521545), and rpoB (KM521546). The 16S rRNA sequence (KM521542) amplified by primers 27f and 1492r shared 99% identity with that of P. anthophila M19_2C (JN644500). P. anthophila was previously reclassified from P. agglomerans (3); therefore, we suggest naming this wampee pathogen P. anthophila. Subsequently, 10 wampee fruits were injected with 20 μl of bacterial suspension (1 × 108 CFU/ml) of strains CL1 and CL2, respectively, and another 10 were injected with 20 μl of LB medium as controls, all kept at 28°C for 4 days. Symptoms similar to those of natural infections were observed on inoculated fruits but not on the negative controls. Bacteria were isolated from diseased tissues and further identified as P. anthophila by gyrB sequencing. P. anthophila was reported to naturally infect balsam and marigold (1,2). To our knowledge, this is the first report of P. anthophila naturally causing soft rot disease and cracking on C. lansium (wampee). References: (1) C. Brady et al. Syst. Appl. Microbiol. 31:447, 2008. (2) C. Brady et al. Int. J. Syst. Evol. Microbiol. 59:2339, 2009. (3) J. Morton. Fruits of Warm Climates. Echo Point Books & Media, Miami, FL, 1987.
  6. Li S, Tao Y, Li D, Wen G, Zhou J, Manickam S, et al.
    Chemosphere, 2021 Aug;276:130090.
    PMID: 33740651 DOI: 10.1016/j.chemosphere.2021.130090
    In this study, 4 Lactobacillus plantarum strains and 5 Lactobacillus fermentum strains adapting well to the unfavorable fruit system were isolated under different fruit environments. The fermentation ability of these autochthonous lactic acid bacteria (LAB) strains in blueberry juice, and the influence of microbial metabolism on juice composition were explored. After 48 h of fermentation, the viable cell counts exceeded 10.0 log CFU/mL, malic acid content decreased from 511.47 ± 10.50 mg/L to below 146.38 ± 3.79 mg/L, and lactic acid content increased from 0 mg/L to above 2184.90 ± 335.80 mg/L. Moreover, the metabolism of these strains exerted a profound influence on the phenolic composition of juice. Total phenolic content in blueberry juice increased by 6.1-81.2% under lactic acid fermentation, and the antioxidant capacity in vitro enhanced by at least 34.0%. Anthocyanin content showed a declining trend, while the profile of non-anthocyaninic phenolics exhibited complex changes. The increments of rutin, myricetin and gallic acid contents through 48 h lactic acid fermentation exceeded 136%, 71% and 38%, respectively. Instead, the contents of p-hydroxybenzoic acid and caffeic acid decreased with fermentation. Overall, Lactobacillus plantarum LSJ-TY-HYB-T9 and LSJ-TY-HYB-T7, and Lactobacillus fermentum LSJ-TY-HYB-C22 and LSJ-TY-HYB-L16 could be the suitable strains to produce fermented fruit juices, including blueberry in practical applications.
  7. Wu Y, Li S, Tao Y, Li D, Han Y, Show PL, et al.
    Food Chem, 2021 Jun 30;348:129083.
    PMID: 33517000 DOI: 10.1016/j.foodchem.2021.129083
    In this study, three potential probiotic strains were selected to ferment blueberry and blackberry juices. The viable cell counts of selected strains were increased by 0.4-0.7 log CFU/mL in berry juices environments after 48-h fermentation. Meanwhile, the contents of cyanindin-3-glucoside and peonidin-3-glucoside decreased over 30%. Heatmap presented an upgrade trend of syringic acid, ferulic acid, gallic acid and lactic acid during fermentation. However, the contents of p-coumaric acid, protocatechuic acid, chlorogenic acid, critic acid and malic acid showed downgrade trend. The metabolism of phenolics probably contributed to the enhancement of the ABTS radical scavenging activity (40%-60%) in fermented berry juices. Moreover, the three strains presented different capacities on changing the quality of berry juices according to the PCA and LDA analysis. The contents of individual organic acids had positive correlations with sensory quality, especially for sourness. Overall, probiotic fermentation could improve the sensory quality of berry juices.
  8. Sheng J, Gong L, Zhou J
    Front Psychol, 2023;14:1103109.
    PMID: 36814667 DOI: 10.3389/fpsyg.2023.1103109
    This study explored the influence of the exercise health belief model and peer support on university students' physical activity PA and clarified the related mechanism. Three hundred and thirty-six healthy university students (aged 19.4 ± 1.3 years, 166 male and 170 female) from Sichuan University of Arts and Science in China were evaluated by the peer support scale, the health belief model scale for exercise, and the physical activity scale (short volume). The results showed that the male students' exercise self-efficacy and PA were markedly higher than female university students. Peer support was positively correlated with perceived benefits, exercise self-efficacy, perceived severity, and cues to action, and was adversely associated with perceived objective and subjective barriers. PA was positively correlated with perceived benefits and exercise self-efficacy, and negatively correlated with perceived objective and subjective barriers. Among the components of the exercise health belief model, only exercise self-efficacy was suitable for constructing a structural equation model (SEM) with peer support and PA. The analysis showed that the predictive effect of exercise self-efficacy on PA was more significant than peer support, and exercise self-efficacy played a critical intermediary role. It is worth noting that, in the grouping model, the effect of male college students' exercise self-efficacy on PA was greater than that of female students, and the model fit of male peer support was better than that of female students. Although the impact of peer support on PA was less than that of exercise self-efficacy and the direct effect of peer support was less than the indirect effect, the impact of peer support on the PA of female university students was higher than that of male university students. This study revealed the impact of exercise self-efficacy and peer support on university students' PA and suggested that exercise self-efficacy is the main path to promoting university students' PA, followed by peer support. Peer support could affect university students' PA not only through direct effects but also through indirect effects. This study also suggested that female university students' peer support has a higher impact on PA than male students. Therefore, when formulating physical exercise courses in the future, it is necessary to give more peer support to female university students to compensate for their low exercise self-efficacy.
  9. Zhang W, Huang G, Ng K, Ji Y, Gao B, Huang L, et al.
    Biomater Sci, 2018 Mar 07.
    PMID: 29511758 DOI: 10.1039/c7bm01186e
    Hydrogel particles that can be engineered to compartmentally culture cells in a three-dimensional (3D) and high-throughput manner have attracted increasing interest in the biomedical area. However, the ability to generate hydrogel particles with specially designed structures and their potential biomedical applications need to be further explored. This work introduces a method for fabricating hydrogel particles in an ellipsoidal cap-like shape (i.e., ellipsoidal cap-like hydrogel particles) by employing an open-pore anodic aluminum oxide membrane. Hydrogel particles of different sizes are fabricated. The ability to produce ellipsoidal cap-like magnetic hydrogel particles with controlled distribution of magnetic nanoparticles is demonstrated. Encapsulated cells show high viability, indicating the potential for using these hydrogel particles as structure- and remote-controllable building blocks for tissue engineering application. Moreover, the hydrogel particles are also used as sacrificial templates for fabricating ellipsoidal cap-like concave wells, which are further applied for producing size controllable cell aggregates. The results are beneficial for the development of hydrogel particles and their applications in 3D cell culture.
  10. Li Y, Li S, Wang Y, Zhou J, Yang J, Ma J
    J Fr Ophtalmol, 2021 Dec;44(10):1596-1604.
    PMID: 34454773 DOI: 10.1016/j.jfo.2021.05.005
    BACKGROUND: The main risks for glaucoma are increased intraocular pressure (IOP) and decreased ocular perfusion pressure (OPP). This review aims to examine the potential impact of lower limb isometric resistance exercise on intraocular pressure and ocular perfusion pressure.

    METHOD: A meta-analysis was conducted to determine the potential impact of isometric exercise on IOP and OPP. The literature on the relationship between isometric resistance exercise and IOP was systematically searched according to the "Cochrane Handbook" in the databases of Pubmed, Web of Science, EBSCO, and Scopus through December 31, 2020. The search terms used were "exercise," "train," "isometric," "intraocular pressure," and "ocular perfusion pressure," and the mean differences of the data were analyzed using the Stata 16.0 software, with a 95% confidence interval.

    RESULTS: A total of 13 studies, which included 268 adult participants consisting of 162 men and 106 women, were selected. All the exercise programs that were included were isometric resistance exercises of the lower limbs with intervention times of 1min, 2min, or 6min. The increase in IOP after intervention was as follows: I2=87.1%, P=0.001 using random-effects model combined statistics, SMD=1.03 (0.48, 1.59), and the increase in OPP was as follows: I2=94.5%, P=0.001 using random-effects model combined statistics, SMD=2.94 (1.65, 4.22), with both results showing high heterogeneity.

    CONCLUSION: As isometric exercise may cause an increase in IOP and OPP, therefore, people with glaucoma and related high risk should perform isometric exercise with caution.

  11. Cui J, Zhou J, Peng Y, Chan A, Mao J
    Environ Sci Process Impacts, 2015 Dec;17(12):2082-91.
    PMID: 26515781 DOI: 10.1039/c5em00383k
    A detailed study on the solution chemistry of red soil in South China is presented. Data are collected from two simulated column-leaching experiments with an improved setup to evaluate the effects of atmospheric N deposition (ADN) composition and ADN flux on agricultural soil acidification using a (15)N tracer technique and an in situ soil solution sampler. The results show that solution pH values decline regardless of the increase of the NH4(+)/NO3(-) ratio in the ADN composition or ADN flux, while exchangeable Al(3+), Ca(2+), Mg(2+), and K(+) concentrations increase at different soil depths (20, 40, and 60 cm). Compared with the control, ADN (60 kg per ha per year N, NH4(+)/NO3(-) ratio of 2 : 1) decreases solution pH values, increases solution concentrations of NO3(-)-N, Al(3+), Ca(2+) and Mg(2+) at the middle and lower soil depths, and promotes their removal. NH4(+)-N was not detected in red soil solutions of all the three soil layers, which might be attributed to effects of nitrification, absorption and fixation in farmland red soil. Some of the NO3(-)-N concentrations at 40-60 cm soil depth exceed the safe drinking level of 10 mg L(-1), especially when the ADN flux is beyond 60 kg ha(-1) N. These features are critical for understanding the ADN agro-ecological effects, and for future assessment of ecological critical loads of ADN in red soil farmlands.
  12. Zhou J, Shaikh LH, Neogi SG, McFarlane I, Zhao W, Figg N, et al.
    Hypertension, 2015 May;65(5):1103-10.
    PMID: 25776071 DOI: 10.1161/HYP.0000000000000025
    Common somatic mutations in CACNAID and ATP1A1 may define a subgroup of smaller, zona glomerulosa (ZG)-like aldosterone-producing adenomas. We have therefore sought signature ZG genes, which may provide insight into the frequency and pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients with Conn's syndrome and 7 patients with pheochromocytoma were assayed by the Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time polymerase chain reaction was performed on genes >10-fold upregulated in ZG (compared with zona fasciculata) and >10-fold upregulated in aldosterone-producing adenomas (compared with ZG). DACH1, a gene associated with tumor progression, was further analyzed. The role of DACH1 on steroidogenesis, transforming growth factor-β, and Wnt signaling activity was assessed in the human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective expression of DACH1 in human ZG. Silencing of DACH1 in H295R cells increased CYP11B2 mRNA levels and aldosterone production, whereas overexpression of DACH1 decreased aldosterone production. Overexpression of DACH1 in H295R cells activated the transforming growth factor-β and canonical Wnt signaling pathways but inhibited the noncanonical Wnt signaling pathway. Stimulation of primary human adrenal cells with angiotensin II decreased DACH1 mRNA expression. Interestingly, there was little overlap between our top ZG genes and those in rodent ZG. In conclusion, (1) the transcriptome profile of human ZG differs from rodent ZG, (2) DACH1 inhibits aldosterone secretion in human adrenals, and (3) transforming growth factor-β signaling pathway is activated in DACH1 overexpressed cells and may mediate inhibition of aldosterone secretion in human adrenals.
  13. Nakamura C, Liu MM, Goo YK, Zhang GH, Jia HL, Kumagai A, et al.
    Trop Biomed, 2020 Dec 01;37(4):1029-1037.
    PMID: 33612755 DOI: 10.47665/tb.37.4.1029
    Previously, we have identified a gene encoding thrombospondin-related anonymous protein of Babesia gibsoni (BgTRAP), and have shown that the antisera raised against recombinant BgTRAP expressed in Escherichia coli inhibited the growth of parasites. In the present study, a recombinant vaccinia virus expressing the BgTRAP (VV/BgTRAP) was constructed. A specific band with a molecular mass of 80 kDa, which is similar to that of native BgTRAP on the merozoites of B. gibsoni, was detected in the supernatant of VV/ BgTRAP-infected RK13 cells. Mice inoculated with VV/BgTRAP produced a specific antiBgTRAP response. The antiserum against VV/BgTRAP showed reactivity against the native BgTRAP on parasites. These results indicated that the recombinant vaccinia virus expressing BgTRAP might be a vaccine candidate against canine B. gibsoni infection.
  14. Yan J, Tian C, Zhou J, Bauer AM, Lee Grismer L, Zhou K
    Mitochondrial DNA, 2014 Jun;25(3):181-2.
    PMID: 23631365 DOI: 10.3109/19401736.2013.792066
    We sequenced the complete mitochondrial genome of the Tioman Island rock gecko, Cnemaspis limi, which is known as an endemic species to Malaysia. The complete mitogenome is 16,680 bp in size, consisting of 37 genes coding for 13 proteins, 22 transfer RNAs, two ribosomal RNAs and one control region. The A + T content of the overall base composition of H-strand is 53.09% (T: 23.20%, C: 32.48%, A: 29.89% and G: 14.43%). The major non-coding region (control region) is 1254 bp in length with the A + T content of 55.09% and four replicates of a 76-bp repeat within this region.
  15. Li S, Lu BP, Feng J, Zhou JJ, Xie ZZ, Liang C, et al.
    Trop Biomed, 2020 Dec 01;37(4):852-863.
    PMID: 33612738 DOI: 10.47665/tb.37.4.852
    Fructose-1,6-bisphosphate aldolase (FbA), a well characterized glycometabolism enzyme, has been found to participate in other important processes besides the classic catalysis. To understand the important functions of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis (CsFbAs, CsFbA-1/2/3) in host-parasite interplay, the open reading frames of CsFbAs were cloned into pET30a (+) vector and the resulting recombinant plasmids were transformed into Escherichia coli BL21 (DE3) for expression of the proteins. Purified recombinant CsFbAs proteins (rCsFbAs) were approximately 45.0 kDa on 12% SDS-PAGE and could be probed with each rat anti-rCsFbAs sera by western blotting analysis. ELISA and ligand blot overlay indicated that rCsFbAs of 45.0 kDa as well as native CsFbAs of 39.5 kDa from total worm extracts and excretory-secretory products of Clonorchis sinensis (CsESPs) could bind to human plasminogen, and the binding could be efficiently inhibited by lysine analog ε-aminocaproic acid. Our results suggested that as both the components of CsESPs and the plasminogen binding proteins, three CsFbAs might be involved in preventing the formation of the blood clot so that Clonorchis sinensis could acquire enough nutrients from host tissue for their successful survival and colonization in the host. Our work will provide us with new information about the biological function of three CsFbAs and their roles in hostparasite interplay.
  16. Tripathi M, Singh BK, Liehn EA, Lim SY, Tikno K, Castano-Mayan D, et al.
    Autophagy, 2022 Sep;18(9):2150-2160.
    PMID: 35012409 DOI: 10.1080/15548627.2021.2021494
    Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an in vivo vascular injury model of restenosis. Furthermore, we studied the effects of caffeine in primary human and mouse aortic VSMCs and immortalized mouse aortic VSMCs. Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells. Genetic deletion of the key autophagy gene Atg5, and the Sqstm1/p62 gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy. Interestingly, caffeine also decreased WNT-signaling and the expression of two WNT target genes, Axin2 and Ccnd1 (cyclin D1). This effect was mediated by autophagic degradation of a key member of the WNT signaling cascade, DVL2, by caffeine to decrease WNT signaling and cell proliferation. SQSTM1/p62, MAP1LC3B-II and DVL2 were also shown to interact with each other, and the overexpression of DVL2 counteracted the inhibition of cell proliferation by caffeine. Taken together, our in vivo and in vitro findings demonstrated that caffeine reduced VSMC proliferation by inhibiting WNT signaling via stimulation of autophagy, thus reducing the vascular restenosis. Our findings suggest that caffeine and other autophagy-inducing drugs may represent novel cardiovascular therapeutic tools to protect against restenosis after angioplasty and/or stent placement.
  17. Qin S, Chen M, Cheng AL, Kaseb AO, Kudo M, Lee HC, et al.
    Lancet, 2023 Nov 18;402(10415):1835-1847.
    PMID: 37871608 DOI: 10.1016/S0140-6736(23)01796-8
    BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.

    METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098.

    FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.

    INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.

    FUNDING: F Hoffmann-La Roche/Genentech.

  18. Zhou J, Wu C, Yeh PJ, Ju J, Zhong L, Wang S, et al.
    Sci Total Environ, 2023 Sep 01;889:164274.
    PMID: 37209749 DOI: 10.1016/j.scitotenv.2023.164274
    The successive flood-heat extreme (SFHE) event, which threatens the securities of human health, economy, and building environment, has attracted extensive research attention recently. However, the potential changes in SFHE characteristics and the global population exposure to SFHE under anthropogenic warming remain unclear. Here, we present a global-scale evaluation of the projected changes and uncertainties in SFHE characteristics (frequency, intensity, duration, land exposure) and population exposure under the Representative Concentration Pathway (RCP) 2.6 and 6.0 scenarios, based on the multi-model ensembles (five global water models forced by four global climate models) within the Inter-Sectoral Impact Model Intercomparison Project 2b framework. The results reveal that, relative to the 1970-1999 baseline period, the SFHE frequency is projected to increase nearly globally by the end of this century, especially in the Qinghai-Tibet Plateau (>20 events/30-year) and the tropical regions (e.g., northern South America, central Africa, and southeastern Asia, >15 events/30-year). The projected higher SFHE frequency is generally accompanied by a larger model uncertainty. By the end of this century, the SFHE land exposure is expected to increase by 12 % (20 %) under RCP2.6 (RCP6.0), and the intervals between flood and heatwave in SFHE tend to decrease by up to 3 days under both RCPs, implying the more intermittent SFHE occurrence under future warming. The SFHE events will lead to the higher population exposure in the Indian Peninsula and central Africa (<10 million person-days) and eastern Asia (<5 million person-days) due to the higher population density and the longer SFHE duration. Partial correlation analysis indicates that the contribution of flood to the SFHE frequency is greater than that of heatwave for most global regions, but the SFHE frequency is dominated by the heatwave in northern North America and northern Asia.
  19. Wu C, Zhong L, Yeh PJ, Gong Z, Lv W, Chen B, et al.
    Sci Total Environ, 2024 Jan 01;906:167632.
    PMID: 37806579 DOI: 10.1016/j.scitotenv.2023.167632
    Drought affects vegetation growth to a large extent. Understanding the dynamic changes of vegetation during drought is of great significance for agricultural and ecological management and climate change adaptation. The relations between vegetation and drought have been widely investigated, but how vegetation loss and restoration in response to drought remains unclear. Using the standardized precipitation evapotranspiration index (SPEI) and the normalized difference vegetation index (NDVI) data, this study developed an evaluation framework for exploring the responses of vegetation loss and recovery to meteorological drought, and applied it to the humid subtropical Pearl River basin (PRB) in southern China for estimating the loss and recovery of three vegetation types (forest, grassland, cropland) during drought using the observed NDVI changes. Results indicate that vegetation is more sensitive to drought in high-elevation areas (lag time  8 months). Vegetation loss (especially in cropland) is found to be more sensitive to drought duration than drought severity and peak. No obvious linear relationship between drought intensity and the extent of vegetation loss is found. Regardless of the intensity, drought can cause the largest probability of mild loss of vegetation, followed by moderate loss, and the least probability of severe loss. Large spatial variability in the probability of vegetation loss and recovery time is found over the study domain, with a higher probability (up to 50 %) of drought-induced vegetation loss and a longer recovery time (>7 months) mostly in the high-elevation areas. Further analysis suggests that forest shows higher but cropland shows lower drought resistance than other vegetation types, and grassland requires a shorter recovery time (4.2-month) after loss than forest (5.1-month) and cropland (4.8-month).
  20. Feng S, Xie X, Liu J, Li A, Wang Q, Guo D, et al.
    J Nanobiotechnology, 2023 Oct 10;21(1):370.
    PMID: 37817254 DOI: 10.1186/s12951-023-02139-z
    Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae.
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