Publications by authors named "Liang Guo"

946 Publications

[Application of chronological lifespan in the construction of Escherichia coli cell factories].

Sheng Wu Gong Cheng Xue Bao 2021 Apr;37(4):1277-1286

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.

Microbial cell factories capable of producing valuable chemicals from renewable feedstocks provide a promising alternative towards sustainability. However, environmental stress remarkably affects the performance of microbial cell factories. By extending the chronological lifespan of microbial cells, the performance of microbial cell factories can be greatly improved. Firstly, an evaluation system for chronological lifespan and semi-chronological lifespan was established based on the changes in survival rates. Secondly, the addition of anti-aging drugs such as cysteine, carnosine, aminoguanidine and glucosamine increased the chronological lifespan of E. coli by 80%, 80%, 50% and 120%, respectively. Finally, we demonstrated that extending the chronological lifespan of E. coli increased the yield of metabolites produced by E. coli cell factories with endogenous (lactic acid and pyruvic acid) or exogenous (malic acid) metabolic pathway by 30.0%, 25.0%, and 27.0%, respectively. The strategy of extending chronological lifespan of E. coli provides a potential approach for enhancing the performance of microbial cell factories.
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http://dx.doi.org/10.13345/j.cjb.200430DOI Listing
April 2021

Nonspecific phospholipase C4 hydrolyzes phosphosphingolipids and sustains plant root growth during phosphate deficiency.

Plant Cell 2021 May;33(3):766-780

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, Hubei, China.

Phosphate is a vital macronutrient for plant growth, and its availability in soil is critical for agricultural sustainability and productivity. A substantial amount of cellular phosphate is used to synthesize phospholipids for cell membranes. Here, we identify a key enzyme, nonspecific phospholipase C4 (NPC4) that is involved in phosphosphingolipid hydrolysis and remodeling in Arabidopsis during phosphate starvation. The level of glycosylinositolphosphorylceramide (GIPC), the most abundant sphingolipid in Arabidopsis thaliana, decreased upon phosphate starvation. NPC4 was highly induced by phosphate deficiency, and NPC4 knockouts in Arabidopsis decreased the loss of GIPC and impeded root growth during phosphate starvation. Enzymatic analysis showed that NPC4 hydrolyzed GIPC and displayed a higher activity toward GIPC as a substrate than toward the common glycerophospholipid phosphatidylcholine. NPC4 was associated with the plasma membrane lipid rafts in which GIPC is highly enriched. These results indicate that NPC4 uses GIPC as a substrate in planta and the NPC4-mediated sphingolipid remodeling plays a positive role in root growth in Arabidopsis response to phosphate deficiency.
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http://dx.doi.org/10.1093/plcell/koaa054DOI Listing
May 2021

Hepatic SENP2 Controls Systemic Metabolism via SUMOylation-dependent Regulation of Liver-Adipose Tissue Crosstalk.

Hepatology 2021 May 2. Epub 2021 May 2.

Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), characterized by aberrant triglycerides accumulation in liver, affects the metabolism remodeling of hepatic and non-hepatic tissues by secreting altered hepatokines. SUMO-specific protease 2 (SENP2) is responsible for de-SUMOylation of target protein, with broad effects on cell growth, signal transduction and developmental process. However, role of SENP2 in hepatic metabolism remains unclear.

Approach & Results: Herein, we found that SENP2 was the most dramatically increased SENPs in the fatty liver, and its level was modulated by fed/fasted conditions. To define the role of hepatic SENP2 in metabolic regulation, we generated liver-specific SENP2 knockout (Senp2-LKO) mice. Senp2-LKO mice exhibited resistance to HFD-induced hepatic steatosis and obesity. RNA-seq analysis showed that Senp2 deficiency upregulated genes involved in fatty acid oxidation and downregulated genes in lipogenesis in the liver. Additionally, ablation of hepatic SENP2 activated thermogenesis of adipose tissues. Improved energy homeostasis of both the liver and adipose tissues by SENP2 disruption prompted us to detect the hepatokines, with FGF21 identified as a key factor markedly elevated in Senp2-LKO mice that maintained metabolic homeostasis. Loss of FGF21 obviously reversed the positive effects of SENP2 deficiency on metabolism. Mechanistically, by screening transcriptional factors of FGF21, PPARα was defined as the mediator for SENP2 and FGF21. SENP2 interacted with PPARα and deSUMOylated it, thereby promoting ubiquitylation and subsequent degradation of PPARα, which in turn inhibited FGF21 expression and fatty acid oxidation. Consistently, SENP2 overexpression in liver facilitated development of metabolic disorders.

Conclusions: Our finding demonstrated key role of hepatic SENP2 in governing metabolic balance by regulating liver-adipose tissue crosstalk, linking the SUMOylation process to metabolic regulation.
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http://dx.doi.org/10.1002/hep.31881DOI Listing
May 2021

Transcriptome Analysis Reveals Genes of Flooding-Tolerant and Flooding-Sensitive Rapeseeds Differentially Respond to Flooding at the Germination Stage.

Plants (Basel) 2021 Apr 3;10(4). Epub 2021 Apr 3.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.

Flooding results in significant crop yield losses due to exposure of plants to hypoxic stress. Various studies have reported the effect of flooding stress at seedling establishment or later stages. However, the molecular mechanism prevailing at the germination stage under flooding stress remains enigmatic. The present study highlights the comparative transcriptome analysis in two rapeseed lines, i.e., flooding-tolerant (Santana) and -sensitive (23651) lines under control and 6-h flooding treatments at the germination stage. A total of 1840 up-regulated and 1301 down-regulated genes were shared by both lines in response to flooding. There were 4410 differentially expressed genes (DEGs) with increased expression and 4271 DEGs with reduced expression shared in both control and flooding conditions. Gene ontology (GO) enrichment analysis revealed that "transcription regulation", "structural constituent of cell wall", "reactive oxygen species metabolic", "peroxidase", oxidoreductase", and "antioxidant activity" were the common processes in rapeseed flooding response. In addition, the processes such as "hormone-mediated signaling pathway", "response to organic substance response", "motor activity", and "microtubule-based process" are likely to confer rapeseed flooding resistance. Mclust analysis clustered DEGs into nine modules; genes in each module shared similar expression patterns and many of these genes overlapped with the top 20 DEGs in some groups. This work provides a comprehensive insight into gene responses and the regulatory network in rapeseed flooding stress and provides guidelines for probing the underlying molecular mechanisms in flooding resistance.
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http://dx.doi.org/10.3390/plants10040693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065761PMC
April 2021

Effect of aerobic/anoxic duration on the performance, microbial activity and microbial community of sequencing batch biofilm reactor treating synthetic mariculture wastewater.

Bioresour Technol 2021 Apr 22;333:125198. Epub 2021 Apr 22.

Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, Qingdao 266100, China.

The effect of aerobic/anoxic duration on the performance, microbial community and enzymatic activity of sequencing batch biofilm reactor (SBBR) were investigated in treating mariculture wastewater. The microbial oxygen uptake rate and nitrifying rate gradually decreased with the aerobic/anoxic duration from 120/210 to 30/300 min, whereas the nitrite reducing rate and nitrate reducing rate had the opposite results. The activities of dehydrogenase, ammonia monooxygenase and nitrite oxidoreductase gradually decreased with the aerobic/anoxic duration from 120/210 to 30/300 min, but the activities of nitrate reductase and nitrite reductase had a gradual increment. The microbial nitrogen removal rates had similar changing trends to their corresponding enzymatic activities at different aerobic/anoxic duration. The variation of aerobic/anoxic duration obviously affected the microbial richness and diversity of SBBR. The co-occurrence, keystone taxa and significant difference of microbial community had some changes with the aerobic/anoxic duration from 120/210 to 30/300 min.
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http://dx.doi.org/10.1016/j.biortech.2021.125198DOI Listing
April 2021

TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR4 Interacts with WRINKLED1 to Mediate Seed Oil Biosynthesis.

Plant Physiol 2020 Oct;184(2):658-665

School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.

Cross-family transcription factor (TF) interactions play critical roles in the regulation of plant developmental and metabolic pathways. WRINKLED1 (WRI1) is a key TF governing oil biosynthesis in plants. However, little is known about WRI1-interacting factors and their roles in oil biosynthesis. We screened a TF library using Arabidopsis (Arabidopsis thaliana) WRI1 (AtWRI1) as bait in yeast two-hybrid assays and identified three TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) family TFs, namely TCP4, TCP10, and TCP24, as AtWRI1-interacting partners. The physical interaction between AtWRI1 and TCPs was further validated using bimolecular fluorescence complementation assays. TCPs play important roles in various plant developmental processes; however, their involvement in fatty acid biosynthesis was not previously known. Coexpression of TCP4, but not TCP10 or TCP24, with AtWRI1 reduced AtWRI1-mediated oil biosynthesis in Nicotiana benthamiana leaves. Transcriptomic analysis in transgenic Arabidopsis plants with enhanced TCP4 activity engineered by expressing rTCP4 (i.e. miR319-resistant TCP4) revealed that AtWRI1 target genes were significantly repressed. TCP4 expression is strongly correlated with AtWRI1 during embryo development. A tcp4 loss-of-function mutant, the jaw-D mutant with a strong reduction of TCP4 expression, and a tcp2 tcp4 tcp10 triple mutant accumulated more seed oil than wild-type Arabidopsis. In addition, TCP4 repressed the AtWRI1-mediated transactivation of the promoters of fatty acid biosynthetic genes. Collectively, our findings suggest that TCP4 represses fatty acid biosynthetic gene expression through interaction with AtWRI1, leading to a reduction of AtWRI1-mediated seed oil accumulation.
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http://dx.doi.org/10.1104/pp.20.00547DOI Listing
October 2020

Linggui Zhugan Decoction for peripheral vertigo: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(16):e25563

Nanchang Hongdu Hospital of Traditional Chinese Medicine.

Background: Vertigo is a sense of movement or rotation of the patient's own or an external object. At present, western medicine treatment such as vestibular suppressant medications commonly used in clinical practice are ineffective and have adverse reactions. In traditional Chinese medicine, Linggui Zhugan Decoction (LZD) was used by doctors to warm yang for resolving fluid retention, strengthen the spleen and clear away dampness, with significant effect. Recently, some clinical studies have also shown that LZD has reliable effect in treating peripheral vertigo, but there is no systematic evidence. Therefore, this study aims to objectively evaluate the efficacy and safety of LZD in the treatment of peripheral vertigo.

Methods: Eight electronic databases will be searched from inception to August 2020 by 2 independent researchers, in order to collect qualified randomized controlled trials (RCTs) on the LZD treatment for peripheral vertigo. The therapeutic effects according to Clinical efficacy will be adopted as the primary outcomes. RevMan V.5.3 software will be used for the data synthesis and the Cochrane's risk of bias assessment tool will be used to assess the risk of bias.

Results: This review will conduct a high-quality synthesis on present evidence of LZD for peripheral vertigo.

Conclusion: The conclusion of the study will indicate whether LZD is an effective treatment for peripheral vertigo by providing updated evidence.

Prospero Registration Number: PROSPERO CRD 42021238817.
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http://dx.doi.org/10.1097/MD.0000000000025563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078309PMC
April 2021

Paradise™ Ultrasound Renal Denervation System for the treatment of hypertension.

Future Cardiol 2021 Apr 20. Epub 2021 Apr 20.

CVPath Institute, Inc., Gaithersburg, MD, USA.

Catheter-based renal denervation is a novel treatment approach for patients with hypertension and initial unblinded trials have shown promising results. The Paradise™ Ultrasound Renal Denervation System (ReCor Medical, CA, USA) is an ultrasound-based catheter with a distal balloon that acts as a coolant to protect the renal arterial wall. This device received CE-mark in 2012. Randomized, sham-controlled trials and postmarket studies have shown promising efficacy and safety results. Currently, three additional ongoing randomized, sham-controlled trials are underway in the USA, Europe, Japan and Korea, and the results will be pivotal in device approval in some of these countries. These studies with larger numbers of patients and longer duration of follow-up are needed to further confirm the safety and efficacy of this device.
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http://dx.doi.org/10.2217/fca-2020-0228DOI Listing
April 2021

L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice.

Diabetes 2021 Apr 16. Epub 2021 Apr 16.

Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical, Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China.

L-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with L-Theanine(100mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1 and other thermogenic genes. Meanwhile, administration of the mice with L-Theanine increased energy expenditure. In vitro studies indicated that L-Theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of L-Theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. L-Theanine treatment enhanced AMPKα phosphorylation both in adipocytes and in iWAT. Knockdown of AMPKα ablolished L-Theanine-induced upregulation of Prdm16 and adipocytes browning. L-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for L-Theanine-induced increase of α-KG and DNA demethylation on Prdm16 promoter. Moreover, intraperitoneal administration with L-Theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol and free fatty acid in the high fat diet-fed mice. Our results suggest a potential role of L-Theanine in combating diet-induced obesity in mice, which may involve L-Theanine-induced browning of white adipose tissue.
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http://dx.doi.org/10.2337/db20-1210DOI Listing
April 2021

Effects of simulated COVID-19 cytokine storm on stent thrombogenicity.

Cardiovasc Revasc Med 2021 Apr 8. Epub 2021 Apr 8.

CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD 20878, United States of America. Electronic address:

Background: Cytokine storm-related hypercoagulation may be important in the pathogenesis of stent thrombosis in patients with SARS-CoV-2. Whether stent polymers behave differently under such conditions has never been explored.

Methods: Fluorinated polymer-nanocoated and uncoated COBRA stents (CeloNova), BioLinx-polymer-coated Resolute Onyx stents (Medtronic), and Synergy stents (Boston Scientific), which are abluminally coated with a bioabsorbable polymer, were exposed to human blood from healthy donors which was supplemented with 400 pg/mL IL-6 and 100 pg/mL TNF-α, similar to what is seen in cytokine storm caused by SARS-CoV-2. Platelet adhesion and neutrophil activation, assessed by immunofluorescence, were compared under cytokine storm and control conditions (untreated blood) (n = 4 experimental runs).

Results: Platelet adhesion values, defined as %platelet-covered area x staining intensity, were significantly lower in coated and uncoated COBRA and in Resolute Onyx than in Synergy under control conditions (1.28 × 10 ± 0.43 × 10 vs. 2.92 × 10 ± 0.49 × 10 vs. 3.57 × 10 ± 0.73 × 10 vs. 9.94 × 10 ± 0.99 × 10; p ≤0.0001). In cytokine storm, platelet adhesion values remained low in coated COBRA-PzF (1.78 × 10 ± 0.38 × 10) compared to all other devices (uncoated COBRA: 5.92 × 10 ± 0.96 × 10; Resolute Onyx: 7.27 × 10 ± 1.82 × 10; Synergy: 11.28 × 10 ± 1.08 × 10; p ≤ 0.0001). Although cytokine storm conditions significantly increased neutrophil activation in all stents, it was significantly less in coated and uncoated COBRA, and in Resolute Onyx than in Synergy.

Conclusions: Blood-biomaterials interactions may determine the thrombogenic potential of stents. Under simulated cytokine storm conditions, fluoropolymer-coated stents showed the most favorable anti-thrombogenic and anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.carrev.2021.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026249PMC
April 2021

A snapshot study of the microbial community dynamics in naturally fermented cow's milk.

Food Sci Nutr 2021 Apr 16;9(4):2053-2065. Epub 2021 Feb 16.

Xilingol Vocational College Xilin Gol Institute of Bioengineering Xilin Gol Food Testing and Risk Assessment Center Xilinhot China.

Natural fermentation of milk is a prerequisite in the production of traditional dairy products and is considered a bioresource of fermentative microorganisms and probiotics. To understand the microbial dynamics during distinct fermentative phases, the roles of different microbes, and the relationship between bacteria and fungi, microbial community dynamics was investigated by culture-dependent and culture-independent approaches. Natural, static fermentation of milk induces the formation of the underlying curds and the superficial sour cream (Zuohe in the Mongolian language). From an overall perspective, viable LAB increased remarkably. Yeast showed an initial increase in their abundance (from 0 hr to 24 hr), which was followed by a decrease, and mold was detected at the later stages of fermentation (after 68 hr). The observed trends in microbiota variation suggest an antagonistic interaction between bacteria (LAB) and fungi (yeast and mold). The beneficial bacterial and fungal genus and species (e.g., , , , , , ) are gradually increased in concentration, and the potentially detrimental microbial genus and species (e.g., , , , , , , ) decrease during the decline of bacterial and fungi diversity from natural fermentation. The study of microbial community dynamics could make a great contribution to understand the mechanism of natural fermentation of milk and the formation of curds and Zuohe, and to discover the potentially fermentative microbes for industrial starter cultures.
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http://dx.doi.org/10.1002/fsn3.2174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020932PMC
April 2021

A chromosome-level genome assembly of the yellowfin seabream (Acanthopagrus latus; Hottuyn, 1782) provides insights into its osmoregulation and sex reversal.

Genomics 2021 Apr 9;113(4):1617-1627. Epub 2021 Apr 9.

Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, Guangdong Province, PR China; Tropical Aquaculture Research and Development Center, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Sanya 572018, China; Guangdong Provincial Engineer Technology Research Center of Marine Biological Seed Industry, Guangzhou, Guangdong Province, PR China; Sanya Tropical Fisheries Research Institute, Sanya, Hainan Province, China. Electronic address:

The yellowfin seabream Acanthopagrus latus is the economically most important Sparidae fish in the northern South China Sea. As euryhaline fish, they are perfect model for investigating osmoregulatory mechanisms in teleosts. Moreover, the reproductive biology of hermaphrodites has long been intriguing; however, little information is known about the molecular pathways underlying their sex change. Here, we report a chromosome level reference genome of A. latus generated by employing the PacBio single molecule sequencing technique (SMRT) and high-throughput chromosome conformation capture (Hi-C) technologies. The draft genome of yellowfin seabream was 806 Mb, with 732 Mb scaffolds anchored on 24 chromosomes. The contig N50 and scaffold N50 were 2.6 Mb and 30.17 Mb, respectively. The assembly is of high integrity and includes 92.23% universal single-copy orthologues based on benchmarking universal single-copy orthologs (BUSCO) analysis. A total of 19,631 protein-coding genes were functionally annotated in the reference genome. Moreover, ARRDC3 and GSTA gene families which related to osmoregulation underwent an extensive expansion in two euryhaline sparids fish genomes compared to other teleost genomes. Moreover, integrating sex-specific transcriptome analyses, several genes related to the transforming growth factor beta (TGF-β) signalling pathway involved in sex differentiation and development. This genomic resource will not only be valuable for studying the osmoregulatory mechanisms in estuarine fish and sex determination in hermaphrodite vertebrate species, but also provide useful genomic tools for facilitating breeding of the yellowfin seabream.
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http://dx.doi.org/10.1016/j.ygeno.2021.04.017DOI Listing
April 2021

Enhancing microalgae growth and product accumulation with carbon source regulation: New perspective for the coordination between photosynthesis and aerobic respiration.

Chemosphere 2021 Mar 31;278:130435. Epub 2021 Mar 31.

College of Environmental Science and Engineering, Ocean University of China, Qingdao, 266100, China.

The coordination between photosynthesis and aerobic respiration under mixotrophic cultivation can make a difference to the growth and biochemical composition of microalgae. However, the response of carbon metabolism to carbon source composition under mixotrophic microalgae cultivation has not been well studied. In this study, the synergistic effects of inorganic carbon (IC) and organic carbon (OC) supply on the growth and carbon metabolism of Chlorella vulgaris under mixotrophic cultivation were investigated. The increase of the proportion of HCO had a positive effect on the expression of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), which promoted the biomass production and carbon fixing. The activity of citrate synthase was attenuated with the increase of IC/OC ratio, indicating that the energy needed for the biomass production in groups with high IC/OC ratio was contributed by photoreaction. Biochemical analysis showed that CO was more efficient than HCO for carbohydrate and lipid accumulation of Chlorella vulgaris, and the highest amount of carbohydrate (30.2%) and lipid (35.8%) was recorded with the combined use of CO and glucose. The results could provide a new perspective on carbon metabolism and enzyme regulation in mixotrophic microalgae cultivation.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130435DOI Listing
March 2021

Comparing the Value of Cystatin C and Serum Creatinine for Evaluating the Renal Function and Predicting the Prognosis of COVID-19 Patients.

Front Pharmacol 2021 22;12:587816. Epub 2021 Mar 22.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan-Meier survival, and curve fitting analyses. When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity ( < 0.001), and elevated creatinine levels were independent predictors of death ( = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels ( < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death.
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http://dx.doi.org/10.3389/fphar.2021.587816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019901PMC
March 2021

Adiabatic evolution of optical beams in nonlocal nonlinear media of gradual nonlocality.

Opt Express 2021 Mar;29(6):9618-9623

We theoretically investigate the evolution of optical beams in nonlocal nonlinear media of gradual nonlocality, which is governed by the nonlocal nonlinear Schrödinger equation with variable coefficient. With the variational approach, the evolution equation of beam width is derived. When the characteristic length of response function gradually changes with any functional forms, beams can exhibit a kind of adiabatic evolution. The variational results are well confirmed by numerical simulations.
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http://dx.doi.org/10.1364/OE.419118DOI Listing
March 2021

Strained Epitaxy of Monolayer Transition Metal Dichalcogenides for Wrinkle Arrays.

ACS Nano 2021 Apr 5;15(4):6633-6644. Epub 2021 Apr 5.

Department of Materials Science and Engineering, Southern University of Science and Technology (SUSTech), Shenzhen 518055, P. R. China.

Wrinkling two-dimensional (2D) transition metal dichalcogenides (TMDCs) provides a mechanism to adjust the physical and chemical properties as per need. Traditionally, TMDCs wrinkles achieved by transferring exfoliated materials on prestretched polymer suffer from poor control and limited sample area, which significantly hinders desirable applications. Herein, we fabricate large-area monolayer TMDCs wrinkle arrays directly on the -quartz substrate using strained epitaxy. The uniaxial thermal expansion coefficient mismatch between the substrate and TMDCs materials enables the generation of large uniaxial thermal strain. By quenching the TMDCs after growth, this uniaxial thermal strain can be quickly released as a form of wrinkle arrays along the [0001] direction. Using WS as a model system, the size of as-grown wrinkles can be finely modulated within sub-100 nm by changing the quenching temperature. These WS wrinkles can be locally folded and form various multilayer structures with odd layer numbers during the transfer process. Besides, the corrugated structures in WS wrinkles induce significant changes to optical properties including anisotropic Raman response, enhanced photoluminescence, and second harmonic generation emissions. Furthermore, these wrinkle arrays exhibit enhanced chemical reactivity that can be selectively engineered to ribbon arrays with improved electrocatalytic performance. The developed strategy of strained epitaxy here should enable flexibility in the design of more sophisticated 2D-based structures, offering a simple but effective way toward the modulation of properties with enhanced performances.
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http://dx.doi.org/10.1021/acsnano.0c09983DOI Listing
April 2021

Eruptive Calcified Nodules as a Potential Mechanism of Acute Coronary Thrombosis and Sudden Death.

J Am Coll Cardiol 2021 Apr;77(13):1599-1611

CVPath Institute, Gaithersburg, Maryland, USA. Electronic address:

Background: Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied.

Objectives: The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes.

Methods: A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification.

Results: The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs.

Conclusions: Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.
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http://dx.doi.org/10.1016/j.jacc.2021.02.016DOI Listing
April 2021

Nonspecific phospholipase C4 hydrolyzes phosphosphingolipids and sustains plant root growth during phosphate deficiency.

Plant Cell 2021 Jan 13. Epub 2021 Jan 13.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, Hubei, China.

Phosphate is a vital macronutrient for plant growth, and its availability in soil is critical for agricultural sustainability and productivity. A substantial amount of cellular phosphate is used to synthesize phospholipids for cell membranes. Here, we identify a key enzyme, nonspecific phospholipase C4 (NPC4) that is involved in phosphosphingolipid hydrolysis and remodeling in Arabidopsis during phosphate starvation. The level of glycosylinositolphosphorylceramide (GIPC), the most abundant sphingolipid in Arabidopsis thaliana, decreased upon phosphate starvation. NPC4 was highly induced by phosphate deficiency, and NPC4 knockouts in Arabidopsis decreased the loss of GIPC and impeded root growth during phosphate starvation. Enzymatic analysis showed that NPC4 hydrolyzed GIPC and displayed a higher activity toward GIPC as a substrate than toward the common glycerophospholipid phosphatidylcholine. NPC4 was associated with the plasma membrane lipid rafts in which GIPC is highly enriched. These results indicate that NPC4 uses GIPC as a substrate in planta and the NPC4-mediated sphingolipid remodeling plays a positive role in root growth in Arabidopsis response to phosphate deficiency.
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http://dx.doi.org/10.1093/plcell/koaa054DOI Listing
January 2021

Acylation of non-specific phospholipase C4 determines its function in plant response to phosphate deficiency.

Plant J 2021 Apr 1. Epub 2021 Apr 1.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Non-specific phospholipase C (NPC) is involved in plant growth, development and stress responses. To elucidate the mechanism by which NPCs mediate cellular functions, here we show that NPC4 is S-acylated at the C terminus and that acylation determines its plasma membrane (PM) association and function. The acylation of NPC4 was detected using NPC4 isolated from Arabidopsis and reconstituted in vitro. The C-terminal Cys-533 was identified as the S-acylation residue, and the mutation of Cys-533 to Ala-533 in NPC4 (NPC4 ) led to the loss of S-acylation and membrane association of NPC4. The knockout of NPC4 impeded the phosphate deficiency-induced decrease of the phosphosphingolipid glycosyl inositol phosphoryl ceramide (GIPC), but introducing NPC4 to npc4-1 failed to complement this defect, thereby supporting the hypothesis that the non-acylated NPC4 fails to hydrolyze GIPC during phosphate deprivation. Moreover, NPC4 failed to complement the primary root growth in npc4-1 under stress. In addition, NPC4 in Brassica napus was S-acylated and mutation of the S-acylating cysteine residue of BnaC01.NPC4 led to the loss of S-acylation and its membrane association. Together, our results reveal that S-acylation of NPC4 in the C terminus is conserved and required for its membrane association, phosphosphingolipid hydrolysis and function in plant stress responses.
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http://dx.doi.org/10.1111/tpj.15260DOI Listing
April 2021

Refusal of cancer-directed surgery in male breast cancer.

Medicine (Baltimore) 2021 Apr;100(13):e25116

Department of Plastic Surgery.

Abstract: It has been reported that some male breast cancer patients may refuse the recommended surgery, but the incidence rate in the United States is not clear. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with the rejection of such cancer-directed surgery.We collected data on 5860 patients with male breast cancer (MBC) from the Surveillance, Epidemiology, and End Results database, including 50 patients refusing surgery as recommended. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to identify the effects of refusing surgery on cancer-specific survival (CSS) and overall survival (OS). The association between acceptance or rejection of surgery and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age, race, clinical characteristics, and radiation.Of the 5860 patients identified, 50 (0.9%) refused surgery. Old age (≥65: hazard ratio [HR]: 3.056, 95% confidence interval [CI]: 1.738-5.374, P < .0001), higher AJCC stage (III: HR: 3.283, 95% CI: 2.134-5.050, P < .0001, IV: HR: 14.237, 95% CI: 8.367-24.226, P < .0001), progesterone receptor status (negative: HR: 1.633, 95% CI: 1.007-2.648, P = .047) were considered risk factors. Compared with the surgery group, the refusal group was associated with a poorer prognosis in both OS and CSS (χ2 = 94.81, P < .001, χ2 = 140.4, P < .001). Moreover, significant differences were also observed in OS and CSS among 1:3 matched groups (P = .0002, P < .001).Compared with the patients undergoing surgery, the patients who refused the cancer-directed surgery had poor prognosis in the total survival period, particularly in stage II and III. The survival benefit for undergoing surgery remained even after adjustment, which indicates the importance of surgical treatment before an advanced stage for male breast cancer patients.
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http://dx.doi.org/10.1097/MD.0000000000025116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021363PMC
April 2021

Japanese Encephalitis in China in the Period of 1950-2018: From Discovery to Control.

Biomed Environ Sci 2021 Mar;34(3):175-183

Department of Arbovirus, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

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http://dx.doi.org/10.3967/bes2021.024DOI Listing
March 2021

Comparative study of physicochemical composition and microbial community of Khoormog, Chigee, and Airag, traditionally fermented dairy products from Xilin Gol in China.

Food Sci Nutr 2021 Mar 19;9(3):1564-1573. Epub 2021 Jan 19.

Faculty of Life Science and Technology Kunming University of Science and Technology Kunming China.

Due to their outstanding nutritional and functional properties, the traditionally fermented dairy products (TFDP) from camel, mare, and cow gained universal praise during their long history of production. In this study, the physicochemical composition and microbial communities of Khoormog, Chigee, and Airag, the TFDP from Xilin Gol in China, were investigated and compared. The physicochemical analysis revealed a higher content of total solid content, protein, and fat in Khoormog (12.5 ± 1.6%; 4.6 ± 0.7%; 4.4 ± 1.3%) compared to Chigee (7.8 ± 1.3%; 2.1 ± 0.2%; 0.8 ± 0.2%) and Airag (8.9 ± 0.7%; 3.7 ± 0.4%; 1.4 ± 0.5%). All three types of TFDP shared 41.2% of bacterial and 25.4% of fungal OTUs, and 95.34% of bacterial and 95.52% of fungal sequence reads. The bacterial and fungal community consisted of four phyla and five genera, and three phyla and seven genera, respectively. Lastly, predominated in Khoormog, Chigee, and Airag at the genus level, while the dominant fungal genera varied among the samples. In conclusion, the microbial community structures of TFDP from camel, mare, and cow were not significantly different in a definite area (Xilingol region), and Khoormog, Chigee, and Airag bred the common "core microbiota".
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http://dx.doi.org/10.1002/fsn3.2131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958581PMC
March 2021

Smooth Muscle Cell-Specific PKM2 (Pyruvate Kinase Muscle 2) Promotes Smooth Muscle Cell Phenotypic Switching and Neointimal Hyperplasia.

Arterioscler Thromb Vasc Biol 2021 May 11;41(5):1724-1737. Epub 2021 Mar 11.

Department of Internal Medicine, Division of Hematology/Oncology, University of Iowa, Iowa City (M.J., N.D., P.D., M.K.N., S.R.L., A.K.C.).

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062279PMC
May 2021

Associated soil aggregate nutrients and controlling factors on aggregate stability in semiarid grassland under different grazing prohibition timeframes.

Sci Total Environ 2021 Feb 27;777:146104. Epub 2021 Feb 27.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, College of Natural Resources and Environment, Northwest A&F University, Yangling 712100, China; Institute of Soil and Water Conservation, Chinese Academy of Sciences, Ministry of Water Resources, Yangling 712100, China; CAS Center for Excellence in Quaternary Science and Global Change, Chinese Academy of Sciences, Xi'an 710061, China. Electronic address:

Grazing prohibition is an effective measure in improving soil stability and ecological quality. However, only a limited number of studies have been published on the dominant factors that impact soil aggregate stability and their associated effects on nutrient distribution for different size soil aggregates under long-term grazing prohibition management. In this study, we investigated variation in soil aggregate stability and nutrient distribution characteristics in semiarid grassland sites under different grazing prohibition timeframes (0 years [GP0], 11 years [GP11], 26 years [GP26], and 36 years [GP36]). Results showed that organic carbon (C) and total nitrogen (TN) concentrations in soil aggregates decreased at GP11 before progressively increasing and reaching its highest value at GP36, and the total phosphorus (TP) concentration did not change significantly. Most nutrients accumulated in macroaggregates (> 0.25 mm) under grazing prohibition, and the nutrient stoichiometry in soil aggregates increased after 26 years. Compared to the control (GP0), the mean weight diameter (MWD) value of the soil stability index increased at GP11 (21.7%) and decreased at GP26 (18.9%). Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) also showed that the proportion of stable organic C-related functional groups (i.e., alkene-C and aromatic-C) in macroaggregates were higher at GP11 and GP36 than at GP26. Furthermore, principal component analysis (PCA), partial least squares path modeling (PLS-PM), and the relative importance of regressors all showed that glomalin-related soil proteins (GRSP) and nutrients indirectly improved aggregate stability in semiarid grassland through their influence on the GRSP accumulation potential and nutrient stoichiometry. Generally, after 26 years grazing prohibition had a positive effect on soil aggregate stability and nutrient accumulation in the semiarid grassland sites investigated for this study. Results from this study provide a theoretical basis to select appropriate grazing prohibition timeframes under grassland management initiatives to optimize ecological quality measures in semiarid regions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146104DOI Listing
February 2021

Vascular Response of a Polymer-Free Paclitaxel-Coated Stent (Zilver PTX) versus a Polymer-Coated Paclitaxel-Eluting Stent (Eluvia) in Healthy Swine Femoropopliteal Arteries.

J Vasc Interv Radiol 2021 Mar 4. Epub 2021 Mar 4.

CVPath Institute, Gaithersburg, Maryland; Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland. Electronic address:

Purpose: To compare the long-term vascular healing responses of healthy swine iliofemoral arteries treated with a polymer-free paclitaxel-eluting stent (Z-PES, Zilver PTX) or a fluoropolymer-based paclitaxel-eluting stent (FP-PES, Eluvia).

Materials And Methods: Bilateral iliofemoral arteries in 20 swine were treated with a Z-PES (n = 16) or a FP-PES (n = 24) and were examined histologically at 1, 3, 6, and 12 months.

Results: Morphometric analysis revealed larger external and internal elastic lamina, stent expansion, and lumen area in the FP-PES than in the Z-PES at all timepoints. Luminal narrowing was similar in the 2 groups at 1 month; however, greater stenosis was observed in the Z-PES group at 3 months, with significant regression thereafter, resulting in equivalent stenosis at 6 and 12 months. Greater drug effect and less complete vessel healing were found in the FP-PES group at all timepoints, including greater numbers of malapposed struts with excessive fibrin deposition at 1 and 3 months, than in the Z-PES group. Three of 12 FP-PESs from the 6- and 12-month cohorts also showed circumferential medial disruption with peri-strut inflammation, whereas no abnormal findings were observed in contralateral Z-PESs.

Conclusions: Prolonged paclitaxel release with the presence of a permanent polymer may contribute to the differential vascular responses seen for the Z-PES and FP-PES groups, including medial layer disruption and aneurysmal vessel degeneration that was sometimes observed in the FP-PES group. These distinct features should be confirmed by pathology and in vivo imaging of human superficial femoral arteries to determine their clinical significance.
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http://dx.doi.org/10.1016/j.jvir.2021.02.014DOI Listing
March 2021

Genome-Wide Association Mapping Unravels the Genetic Control of Seed Vigor under Low-Temperature Conditions in Rapeseed ( L.).

Plants (Basel) 2021 Feb 24;10(3). Epub 2021 Feb 24.

MOA Key Lab. of Crop Ecophysiology and Farming System in the Middle Reaches of the Yangtze River/College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Low temperature inhibits rapid germination and successful seedling establishment of rapeseed ( L.), leading to significant productivity losses. Little is known about the genetic diversity for seed vigor under low-temperature conditions in rapeseed, which motivated our investigation of 13 seed germination- and emergence-related traits under normal and low-temperature conditions for 442 diverse rapeseed accessions. The stress tolerance index was calculated for each trait based on performance under non-stress and low-temperature stress conditions. Principal component analysis of the low-temperature stress tolerance indices identified five principal components that captured 100% of the seedling response to low temperature. A genome-wide association study using ~8 million SNP (single-nucleotide polymorphism) markers identified from genome resequencing was undertaken to uncover the genetic basis of seed vigor related traits in rapeseed. We detected 22 quantitative trait loci (QTLs) significantly associated with stress tolerance indices regarding seed vigor under low-temperature stress. Scrutiny of the genes in these QTL regions identified 62 candidate genes related to specific stress tolerance indices of seed vigor, and the majority were involved in DNA repair, RNA translation, mitochondrial activation and energy generation, ubiquitination and degradation of protein reserve, antioxidant system, and plant hormone and signal transduction. The high effect variation and haplotype-based effect of these candidate genes were evaluated, and high priority could be given to the candidate genes , , , and in further study. These findings should be useful for marker-assisted breeding and genomic selection of rapeseed to increase seed vigor under low-temperature stress.
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http://dx.doi.org/10.3390/plants10030426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996214PMC
February 2021

Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells.

Cell Rep Med 2021 Feb 16;2(2):100205. Epub 2021 Feb 16.

Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Persons with HIV are at increased risk for diabetes mellitus compared with individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, and adipose tissue T cells modulate local inflammatory responses and, by extension, adipocyte function. Persons with HIV and diabetes have a high proportion of CX3CR1 GPR56 CD57 (C-G-C) CD4 T cells in adipose tissue, a subset of which are cytomegalovirus specific, whereas individuals with diabetes but without HIV have predominantly CD69 CD4 T cells. Adipose tissue CD69 and C-G-C CD4 T cell subsets demonstrate higher receptor clonality compared with the same cells in blood, potentially reflecting antigen-driven expansion, but C-G-C CD4 T cells have a more inflammatory and cytotoxic RNA transcriptome. Future studies will explore whether viral antigens have a role in recruitment and proliferation of pro-inflammatory C-G-C CD4 T cells in adipose tissue of persons with HIV.
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http://dx.doi.org/10.1016/j.xcrm.2021.100205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897802PMC
February 2021

Effects of salinity on pollutant removal and bacterial community in a partially saturated vertical flow constructed wetland.

Bioresour Technol 2021 Jun 23;329:124890. Epub 2021 Feb 23.

Key Lab of Marine Environment and Ecology, Ministry of Education, Ocean University of China, 266100 Qingdao, China; College of Environmental Science and Engineering, Ocean University of China, 266100 Qingdao, China.

This study investigated the influence of salinity on pollutant removal and bacterial community within a partially saturated vertical flow constructed wetland (PS-VFCW). High removal rates of NH-N (88.29 ± 4.97-100 ± 0%), total inorganic nitrogen (TIN) (50.00 ± 7.21-62.81 ± 7.21%) and COD (91.08 ± 2.66-100 ± 0%) were achieved at 0.4-2.4% salinity levels. The removal of ammonia, TIN and organic matter occurred mainly in unsaturated zone. Salt-adaptable microbes became the dominant bacteria with salinity elevated. The proportion of ammonia-oxidizing bacteria (AOB) in the 0-5 cm depth layer (unsaturated zone) decreased obviously as the salinity increased to 2.4%. Nitrite-oxidizing bacteria (NOB) in the 0-5 cm depth layer showed a decreasing trend with elevated salinity. Denitrifying bacteria (DNB) in the 0-5 cm depth layer maintained high abundance (27.70-53.60%) at 0.4-2.4% salinity levels. At 2.4% salinity, AOB, NOB and DNB were observed in the unsaturated zones and saturated zones, and showed higher abundance in the unsaturated zone.
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http://dx.doi.org/10.1016/j.biortech.2021.124890DOI Listing
June 2021

Treatment of fingertip defect with reversed digital artery island flap through superficial vein anastomosis.

ANZ J Surg 2021 Feb 26. Epub 2021 Feb 26.

Department of Hand Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, China.

Background: This study prospectively explored the clinical effect of a reversed digital artery island flap (RDAIF) in repairing fingertip defects and the impact of the anastomosis of superficial veins in the recipient area on the incidence of venous crisis.

Methods: A total of 92 patients with fingertip defects who underwent RDAIF from February 2016 to February 2018 were enrolled in this prospective, randomized, controlled trial. Of these, 44 patients underwent superficial vein anastomosis. The perioperative data, clinical efficacy and complications of the two groups were compared by the chi-squared test and binary logistic regression analysis.

Results: The average follow-up time was 7.0 ± 2.9 months. The incidence of venous congestion was significantly correlated with flap size, surgical time and anastomosis of superficial veins (Wald = 6.512, 9.353 and 11.662; P = 0.011, 0.002 and 0.001, respectively). The fingertips of the two groups of patients were well repaired, wear resistant and stable in holding, and the two-point discrimination was 5-8 mm.

Conclusion: RDAIF is a safe and effective method for the treatment of fingertip defects, especially in patients who require maintenance of function or contour of the fingertip. Anastomosis of the superficial veins and reduction of the flap area and surgical time can significantly reduce the incidence of venous congestion.
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http://dx.doi.org/10.1111/ans.16698DOI Listing
February 2021

Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms.

Nat Metab 2021 02 22;3(2):166-181. Epub 2021 Feb 22.

Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.

Stable atherosclerotic plaques are characterized by a thick, extracellular matrix-rich fibrous cap populated by protective ACTA2 myofibroblast (MF)-like cells, assumed to be almost exclusively derived from smooth muscle cells (SMCs). Herein, we show that in murine and human lesions, 20% to 40% of ACTA2 fibrous cap cells, respectively, are derived from non-SMC sources, including endothelial cells (ECs) or macrophages that have undergone an endothelial-to-mesenchymal transition (EndoMT) or a macrophage-to-mesenchymal transition (MMT). In addition, we show that SMC-specific knockout of the Pdgfrb gene, which encodes platelet-derived growth factor receptor beta (PDGFRβ), in Apoe mice fed a Western diet for 18 weeks resulted in brachiocephalic artery lesions nearly devoid of SMCs but with no changes in lesion size, remodelling or indices of stability, including the percentage of ACTA2 fibrous cap cells. However, prolonged Western diet feeding of SMC Pdgfrb-knockout mice resulted in reduced indices of stability, indicating that EndoMT- and MMT-derived MFs cannot compensate indefinitely for loss of SMC-derived MFs. Using single-cell and bulk RNA-sequencing analyses of the brachiocephalic artery region and in vitro models, we provide evidence that SMC-to-MF transitions are induced by PDGF and transforming growth factor-β and dependent on aerobic glycolysis, while EndoMT is induced by interleukin-1β and transforming growth factor-β. Together, we provide evidence that the ACTA2 fibrous cap originates from a tapestry of cell types, which transition to an MF-like state through distinct signalling pathways that are either dependent on or associated with extensive metabolic reprogramming.
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http://dx.doi.org/10.1038/s42255-020-00338-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905710PMC
February 2021