Publications by authors named "Yihua Wang"

164 Publications

3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study.

Lancet Respir Med 2021 May 5. Epub 2021 May 5.

Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK. Electronic address:

Background: The consequences of COVID-19 in those who recover from acute infection requiring hospitalisation have yet to be clearly defined. We aimed to describe the temporal trends in respiratory outcomes over 12 months in patients hospitalised for severe COVID-19 and to investigate the associated risk factors.

Methods: In this prospective, longitudinal, cohort study, patients admitted to hospital for severe COVID-19 who did not require mechanical ventilation were prospectively followed up at 3 months, 6 months, 9 months, and 12 months after discharge from Renmin Hospital of Wuhan University, Wuhan, China. Patients with a history of hypertension; diabetes; cardiovascular disease; cancer; and chronic lung disease, including asthma or chronic obstructive pulmonary disease; or a history of smoking documented at time of hospital admission were excluded at time of electronic case-note review. Patients who required intubation and mechanical ventilation were excluded given the potential for the consequences of mechanical ventilation itself to influence the factors under investigation. During the follow-up visits, patients were interviewed and underwent physical examination, routine blood test, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide [DLCO]; forced expiratory flow between 25% and 75% of forced vital capacity [FVC]; functional residual capacity; FVC; FEV; residual volume; total lung capacity; and vital capacity), chest high-resolution CT (HRCT), and 6-min walk distance test, as well as assessment using a modified Medical Research Council dyspnoea scale (mMRC).

Findings: Between Feb 1, and March 31, 2020, of 135 eligible patients, 83 (61%) patients participated in this study. The median age of participants was 60 years (IQR 52-66). Temporal improvement in pulmonary physiology and exercise capacity was observed in most patients; however, persistent physiological and radiographic abnormalities remained in some patients with COVID-19 at 12 months after discharge. We found a significant reduction in DLCO over the study period, with a median of 77% of predicted (IQR 67-87) at 3 months, 76% of predicted (68-90) at 6 months, and 88% of predicted (78-101) at 12 months after discharge. At 12 months after discharge, radiological changes persisted in 20 (24%) patients. Multivariate logistic regression showed increasing odds of impaired DLCO associated with female sex (odds ratio 8·61 [95% CI 2·83-26·2; p=0·0002) and radiological abnormalities were associated with peak HRCT pneumonia scores during hospitalisation (1·36 [1·13-1·62]; p=0·0009).

Interpretation: In most patients who recovered from severe COVID-19, dyspnoea scores and exercise capacity improved over time; however, in a subgroup of patients at 12 months we found evidence of persistent physiological and radiographic change. A unified pathway for the respiratory follow-up of patients with COVID-19 is required.

Funding: National Natural Science Foundation of China, UK Medical Research Council, and National Institute for Health Research Southampton Biomedical Research Centre.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(21)00174-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099316PMC
May 2021

Long-term follow-up and successful treatment of pulmonary alveolar proteinosis without hypercholesterolemia with statin therapy: a case report.

J Int Med Res 2021 Apr;49(4):3000605211010046

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy is a novel treatment for PAP with hypercholesterolemia. However, this treatment has never been described in a patient without hypercholesterolemia. Here, we present a case of successful treatment with atorvastatin for a patient with possibly unclassified PAP without hypercholesterolemia who responded poorly to whole lung lavage therapy and inhaled granulocyte-macrophage colony-stimulating factor. After 18 months of atorvastatin treatment, the patient experienced improvements in dyspnea, radiographic abnormalities and pulmonary function. The present case study supports the feasibility of statin therapy for PAP regardless of the level of cholesterol.
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http://dx.doi.org/10.1177/03000605211010046DOI Listing
April 2021

Post-Golgi Trafficking of Rice Storage Proteins Requires the Small GTPase Rab7 Activation Complex MON1-CCZ1.

Plant Physiol 2021 Apr 19. Epub 2021 Apr 19.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing 210095, China.

Protein storage vacuoles (PSVs) are unique organelles that accumulate storage proteins in plant seeds. Although morphological evidence points to the existence of multiple PSV-trafficking pathways for storage protein targeting, the molecular mechanisms that regulate these processes remain mostly unknown. Here, we report the functional characterization of the rice (Oryza sativa) glutelin precursor accumulation7 (gpa7) mutant, which over-accumulates 57-kD glutelin precursors in dry seeds. Cytological and immunocytochemistry studies revealed that the gpa7 mutant exhibits abnormal accumulation of storage pre-vacuolar compartment-like structures, accompanied by the partial mistargeting of glutelins to the extracellular space. The gpa7 mutant was altered in the CCZ1 locus, which encodes the rice homolog of Arabidopsis (Arabidopsis thaliana) CALCIUM CAFFEINE ZINC SENSITIVITY1a (CCZ1a) and CCZ1b. Biochemical evidence showed that rice CCZ1 interacts with MONENSIN SENSITIVITY1 (MON1) and that these proteins function together as the Rat brain 5 (Rab5) effector and the Rab7 guanine nucleotide exchange factor (GEF). Notably, loss of CCZ1 function promoted the endosomal localization of Vacuolar Protein Sorting-associated protein 9 (VPS9), which is the GEF for Rab5 in plants. Together, our results indicate that the MON1-CCZ1 complex is involved in post-Golgi trafficking of rice storage protein through a Rab5 and Rab7-dependent pathway.
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http://dx.doi.org/10.1093/plphys/kiab175DOI Listing
April 2021

Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial-Mesenchymal Transition.

Front Mol Biosci 2021 19;8:595712. Epub 2021 Mar 19.

Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom.

Alveolar type II (ATII) epithelial cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying a number of lung diseases, including acute injury, fibrosis and cancer, in which signals transduced by RAS and transforming growth factor (TGF)-β play critical roles. To identify downstream molecular events following RAS and/or TGF-β activation, we performed proteomic analysis using a quantitative label-free approach (LC-HDMS) to provide in-depth proteome coverage and estimates of protein concentration in absolute amounts. Data are available via ProteomeXchange with identifier PXD023720. We chose ATII as an experimental cell line in which RAS is activated by adding 4-hydroxytamoxifen (4-OHT). Proteomic analysis of ATII cells treated with 4-OHT or TGF-β demonstrated that RAS activation induces an epithelial-mesenchymal transition (EMT) signature. In contrast, under the same conditions, activation of TGF-β signaling alone only induces a partial EMT. EMT is a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties, and is involved in embryonic development, wound healing, fibrosis and cancer metastasis. Thus, these results could help to focus research on the identification of processes that are potentially driving EMT-related human disease.
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http://dx.doi.org/10.3389/fmolb.2021.595712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048883PMC
March 2021

Identification of the trehalose-6-phosphate synthase gene family in Medicago truncatula and expression analysis under abiotic stresses.

Gene 2021 Jun 18;787:145641. Epub 2021 Apr 18.

College of Biological Sciences and Engineering, Jiangxi Agricultural University, Nanchang 330045, PR China. Electronic address:

Trehalose-6-phosphate synthase (TPS) exerts important functions related to plant desiccation tolerance and responses to environmental stimuli. However, in Medicago truncatula, the TPS family has not been reported to date. This study found 11 MtTPS genes in the genome of M. truncatula, which could be divided into two subfamilies: Class I and Class II. All TPS family members have a TPS domain (Glyco transf_20) at the N-terminus and a TPP domain (Trehalose_PPase) at the C-terminus. Interestingly, the genetic structures differ between Class I and Class II, Class I members have more introns than Class II members. Furthermore, transcriptome and real-time PCR analysis showed that five MtTPS genes could be induced by drought, salt or cold. Specifically, MtTPS2, MtTPS8, MtTPS9, MtTPS11 were up-regulated under both drought and salt treatment, particularly, MtTPS8 and MtTPS9 can also be induced by cold, while MtTPS7 only responded to salt stress. In summary, this study provides the foundation for further research on TPS genes in M. truncatula and their regulatory function in response to abiotic stresses.
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http://dx.doi.org/10.1016/j.gene.2021.145641DOI Listing
June 2021

Treatment response correlation between primary tumor and axillary lymph nodes after neoadjuvant therapy in breast cancer: a retrospective study based on real-world data.

Gland Surg 2021 Feb;10(2):656-669

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Excellent response of the primary tumor after neoadjuvant therapy may indicate a better axillary status in breast cancer. However, this treatment response correlation has not been investigated in Chinese breast cancer patients.

Methods: Patients diagnosed with breast cancer and treated with neoadjuvant therapy were included in this retrospective study, conducted at a comprehensive breast cancer institution in China. Clinicopathological factors at baseline were analyzed by univariate and multivariate analyses. Furthermore, association rules analyses were used to investigate the correlation between the pathologic response of the primary tumor and that of the axillary lymph nodes based on such factors.

Results: Multivariate logistic regression analysis showed that breast pathologic response was influenced by tumor size, classification of regional lymph nodes, histological grade, progesterone receptor status, and Ki67 expression. The potential influencing factor for the pathologic response of the axilla was found to be regional lymph node classification. The findings from association rules analyses demonstrated that when a pathologic complete response (pCR) in the breast was achieved among patients with cTN and hormone receptor-negative disease, the axilla response in these patients was also highly likely to be pCR (the likelihood for axilla pCR was more than 90%). However, cTN patients hardly achieved pCR for both the primary tumor and axillary lymph nodes (mean confidence, 0.9637). The clinicopathological factors accounting for the inconsistent response between the breast and the axilla were found to be hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, and low Ki67 expression.

Conclusions: Our findings suggest a strong correlation between breast pCR and axilla pCR among patients with specific characteristics. These findings provide a basis for the selection of candidates for clinical trials on the omission of axillary surgery.
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http://dx.doi.org/10.21037/gs-20-686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944072PMC
February 2021

ENLARGED STARCH GRAIN1 affects amyloplast development and starch biosynthesis in rice endosperm.

Plant Sci 2021 Apr 28;305:110831. Epub 2021 Jan 28.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing 210095, China; National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Cereal crops accumulate large amounts of starch which is synthesized and stored in amyloplasts in the form of starch grains (SGs). Despite significant progress in deciphering starch biosynthesis, our understanding of amyloplast development in rice (Oryza sativa) endosperm remains largely unknown. Here, we report a novel rice floury mutant named enlarged starch grain1 (esg1). The mutant has decreased starch content, altered starch physicochemical properties, slower grain-filling rate and reduced 1000-grain weight. A distinctive feature in esg1 endosperm is that SGs are much larger, mainly due to an increased number of starch granules per SG. Spherical and loosely assembled granules, together with those weakly stained SGs may account for decreased starch content in esg1. Map-based cloning revealed that ESG1 encodes a putative permease subunit of a bacterial-type ABC (ATP-binding cassette) lipid transporter. ESG1 is constitutively expressed in various tissues. It encodes a protein localized to the chloroplast and amyloplast membranes. Mutation of ESG1 causes defective galactolipid synthesis. The overall study indicates that ESG1 is a newly identified protein affecting SG development and subsequent starch biosynthesis, which provides novel insights into amyloplast development in rice.
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http://dx.doi.org/10.1016/j.plantsci.2021.110831DOI Listing
April 2021

Rice FLOURY SHRUNKEN ENDOSPERM 5 Encodes a Putative Plant Organelle RNA Recognition Protein that Is Required for cis-Splicing of Mitochondrial nad4 Intron 1.

Rice (N Y) 2021 Mar 10;14(1):29. Epub 2021 Mar 10.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

Background: The sequences of several important mitochondrion-encoded genes involved in respiration in higher plants are interrupted by introns. Many nuclear-encoded factors are involved in splicing these introns, but the mechanisms underlying this splicing remain unknown.

Results: We isolated and characterized a rice mutant named floury shrunken endosperm 5 (fse5). In addition to having floury shrunken endosperm, the fse5 seeds either failed to germinate or produced seedlings which grew slowly and died ultimately. Fse5 encodes a putative plant organelle RNA recognition (PORR) protein targeted to mitochondria. Mutation of Fse5 hindered the splicing of the first intron of nad4, which encodes an essential subunit of mitochondrial NADH dehydrogenase complex I. The assembly and NADH dehydrogenase activity of complex I were subsequently disrupted by this mutation, and the structure of the mitochondria was abnormal in the fse5 mutant. The FSE5 protein was shown to interact with mitochondrial intron splicing factor 68 (MISF68), which is also a splicing factor for nad4 intron 1 identified previously via yeast two-hybrid (Y2H) assays.

Conclusion: Fse5 which encodes a PORR domain-containing protein, is essential for the splicing of nad4 intron 1, and loss of Fse5 function affects seed development and seedling growth.
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http://dx.doi.org/10.1186/s12284-021-00463-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947098PMC
March 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

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 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.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Subunit E isoform 1 of vacuolar H+-ATPase OsVHA enables post-Golgi trafficking of rice seed storage proteins.

Plant Physiol 2021 Feb 24. Epub 2021 Feb 24.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing 210095, China.

Dense vesicles (DVs) are Golgi-derived plant-specific carriers that mediate post-Golgi transport of seed storage proteins in angiosperms. How this process is regulated remains elusive. Here, we report a rice (Oryza sativa) mutant, named glutelin precursor accumulation8 (gpa8) that abnormally accumulates 57 kD proglutelins in the mature endosperm. Cytological analyses of the gpa8 mutant revealed that proglutelin-containing DVs were mistargeted to the apoplast forming electron-dense aggregates and paramural bodies (PMB) in developing endosperm cells. Differing from previously reported gpa mutants with post-Golgi trafficking defects, the gpa8 mutant showed bent Golgi bodies, defective trans-Golgi network (TGN), and enlarged DVs, suggesting a specific role of GPA8 in DV biogenesis. We demonstrated that GPA8 encodes a subunit E isoform 1 of vacuolar H+-ATPase (OsVHA-E1) that mainly localizes to TGN and the tonoplast. Further analysis revealed that the luminal pH of the TGN and vacuole is dramatically increased in the gpa8 mutant. Moreover, the colocalization of GPA1 and GPA3 with TGN marker protein in gpa8 protoplasts was obviously decreased. Our data indicated that OsVHA-E1 is involved in endomembrane luminal pH homeostasis as well as maintenance of Golgi morphology and TGN required for DV biogenesis and subsequent protein trafficking in rice endosperm cells.
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http://dx.doi.org/10.1093/plphys/kiab099DOI Listing
February 2021

BRITTLE PLANT1 is required for normal cell wall composition and mechanical strength in rice.

J Integr Plant Biol 2021 May 22;63(5):865-877. Epub 2021 Mar 22.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

A series of nucleotide sugar interconversion enzymes (NSEs) generate the activated sugar donors required for biosynthesis of cell wall matrix polysaccharides and glycoproteins. UDP-glucose 4-epimerases (UGEs) are NSEs that function in the interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal). The roles of UDP-glucose 4-epimerases in monocots remain unclear due to redundancy in the pathways. Here, we report a brittle plant (bp1) rice mutant that exhibits brittle leaves and culms at all growth stages. The mutant culms had reduced levels of rhamnogalacturonan I, homogalacturonan, and arabinogalactan proteins. Moreover, the mutant had altered contents of uronic acids, neutral noncellulosic monosaccharides, and cellulose. Map-based cloning demonstrated that OsBP1 encodes a UDP-glucose 4-epimerase (OsUGE2), a cytosolic protein. We also show that BP1 can form homo- and hetero-protein complexes with other UGE family members and with UDP-galactose transporters 2 (OsUGT2) and 3 (OsUGT3), which may facilitate the channeling of Gal to polysaccharides and proteoglycans. Our results demonstrate that BP1 participates in regulating the sugar composition and structure of rice cell walls.
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http://dx.doi.org/10.1111/jipb.13050DOI Listing
May 2021

The mobilization of splenic reservoir myeloid-derived suppressor cells in sepsis-induced myocardial injury.

Am J Transl Res 2020 15;12(11):7114-7126. Epub 2020 Nov 15.

Department of Cardiology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College Wuhu, Anhui, China.

Background: Myeloid-derived suppressor cells (MDSCs) play key roles in sepsis, but whether the bone marrow is considered the only source remains unclear. The current knowledge about the mechanism of MDSCs leading to myocardial injury in sepsis is poor.

Methods: In sepsis patients with cardiac dysfunction, the circulating percentage of CD14CD11b and serum concentrations of IL-6 and IL-1β were measured. A mouse sepsis model was established through caecum ligation and puncture (CLP). Animals were divided into four groups: control, sham, CLP and CLP+splenectomy (CLPS). Serum concentrations of IL-6, IL-1β, TnI and NT-proBNP were measured. CD11bGr-1 cells were detected by immunofluorescence staining and RT-PCR. Myocardial injury was detected by HE, Masson and TUNEL staining. The expression of mTOR, P53 and caspase-3 was measured by Western blot.

Results: In sepsis patients, circulating MDSCs were increased, and the serum concentrations of IL-6 and IL-1β were elevated. The serum concentrations of IL-6 and IL-1β were correlated with the ratio of circulating MDSCs. In the mouse sepsis model, the spleen was the major source of CD11bGr-1 cells that migrated into circulation and the heart in sepsis. The serum concentrations of IL-6 and IL-1β were also elevated. Echocardiography and serum biomarkers showed that cardiomyocyte damage and cardiac hypofunction in sepsis-induced myocardial injury. The expression of CD11b, Gr-1 and pro-inflammatory cytokines in the heart was significantly higher in sepsis patients than that in controls. Pathological staining and TUNEL staining showed obvious myocardial damage and cell apoptosis. The Western blot analysis indicated that in the heart, the activation of mTOR was inhibited and that the expression of P53 and caspase-3 was elevated in sepsis-induced myocardial injury.

Conclusion: In sepsis-induced myocardial injury, splenic reservoir CD11bGr-1 cells rapidly migrated into circulation and the heart, further impairing heart function via the high expression of P53 through the inhibition of mTOR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724347PMC
November 2020

Rice FLOURY ENDOSPERM 18 encodes a pentatricopeptide repeat protein required for 5' processing of mitochondrial nad5 messenger RNA and endosperm development.

J Integr Plant Biol 2021 May 4;63(5):834-847. Epub 2021 Mar 4.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

Pentatricopeptide repeat (PPR) proteins, composing one of the largest protein families in plants, are involved in RNA binding and regulation of organelle RNA metabolism at the post-transcriptional level. Although several PPR proteins have been implicated in endosperm development in rice (Oryza sativa), the molecular functions of many PPRs remain obscure. Here, we identified a rice endosperm mutant named floury endosperm 18 (flo18) with pleiotropic defects in both reproductive and vegetative development. Map-based cloning and complementation tests showed that FLO18 encodes a mitochondrion-targeted P-type PPR protein with 15 PPR motifs. Mitochondrial function was disrupted in the flo18 mutant, as evidenced by decreased assembly of Complex I in the mitochondrial electron transport chain and altered mitochondrial morphology. Loss of FLO18 function resulted in defective 5'-end processing of mitochondrial nad5 transcripts encoding subunit 5 of nicotinamide adenine dinucleotide hydrogenase. These results suggested that FLO18 is involved in 5'-end processing of nad5 messenger RNA and plays an important role in mitochondrial function and endosperm development.
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http://dx.doi.org/10.1111/jipb.13049DOI Listing
May 2021

The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes.

Biochem Biophys Res Commun 2021 01 3;534:429-435. Epub 2020 Dec 3.

Neurology Department, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. Electronic address:

Slow-wave sleep, defined by low frequency (<4 Hz) electrical brain activity, is a basic brain function affecting metabolite clearance and memory consolidation. The origin of low-frequency activity is related to cortical up and down states, but the underlying cellular mechanism of how low-frequency activities affect metabolite clearance and memory consolidation has remained elusive. We applied electrical stimulation with voltages comparable to in vivo sleep recordings over a range of frequencies to cultured glial astrocytes while monitored the trafficking of GFP-tagged intracellular vesicles using total internal reflection fluorescence microscopy (TIRFM). We found that during low frequency (2 Hz) electrical stimulation the mobility of intracellular vesicle increased more than 20%, but remained unchanged under intermediate (20 Hz) or higher (200 Hz) frequency stimulation. We demonstrated a frequency-dependent effect of electrical stimulation on the mobility of astrocytic intracellular vesicles. We suggest a novel mechanism of brain modulation that electrical signals in the lower range frequencies embedded in brainwaves modulate the functionality of astrocytes for brain homeostasis and memory consolidation. The finding suggests a physiological mechanism whereby endogenous low-frequency brain oscillations enhance astrocytic function that may underlie some of the benefits of slow-wave sleep and highlights possible medical device approach for treating neurological diseases.
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http://dx.doi.org/10.1016/j.bbrc.2020.11.064DOI Listing
January 2021

Transcriptional activation and phosphorylation of OsCNGC9 confer enhanced chilling tolerance in rice.

Mol Plant 2021 02 2;14(2):315-329. Epub 2020 Dec 2.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Low temperature is a major environmental factor that limits plant growth and productivity. Although transient elevation of cytoplasmic calcium has long been recognized as a critical signal for plant cold tolerance, the calcium channels responsible for this process have remained largely elusive. Here we report that OsCNGC9, a cyclic nucleotide-gated channel, positively regulates chilling tolerance by mediating cytoplasmic calcium elevation in rice (Oryza sativa). We showed that the loss-of-function mutant of OsCNGC9 is defective in cold-induced calcium influx and more sensitive to prolonged cold treatment, whereas OsCNGC9 overexpression confers enhanced cold tolerance. Mechanistically, we demonstrated that in response to chilling stress, OsSAPK8, a homolog of Arabidopsis thaliana OST1, phosphorylates and activates OsCNGC9 to trigger Ca influx. Moreover, we found that the transcription of OsCNGC9 is activated by a rice dehydration-responsive element-binding transcription factor, OsDREB1A. Taken together, our results suggest that OsCNGC9 enhances chilling tolerance in rice through regulating cold-induced calcium influx and cytoplasmic calcium elevation.
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http://dx.doi.org/10.1016/j.molp.2020.11.022DOI Listing
February 2021

A Rare Malignant Disease, Dermatofibrosarcoma Protuberans of the Breast: A Retrospective Analysis and Review of Literature.

Biomed Res Int 2020 9;2020:8852182. Epub 2020 Nov 9.

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade fibroblastic mesenchymal tumor derived from the dermis. The aim of this retrospective analysis was to summarize the clinicopathological data from our cases and published cases to offer more evidence for the recognition of dermatofibrosarcoma protuberans (DFSP). A total of 6 breast DFSP patients who had received treatment in our hospital were retrospectively enrolled, and detailed clinicopathological data were gathered for analysis. The median age was 29.5 years (ranging from 17 to 42 years). Most cases presented a red or brown-red, mobile, well-circumscribed, protruding, breast mass (ranging from 1 to 3 cm). For histopathology, all cases (6/6) showed a storiform pattern of spindle cells that were positive for CD34 (6/6) and Vimentin (5/6) and negative for smooth muscle actin (0/6) and S-100 protein (0/6). The majority of patients (5/6) underwent wide local excision, with 2 cases treated with radiotherapy. With a median follow-up of 36 months, all 6 patients survived without recurrence or metastasis. The PubMed database was used to search for similar cases. Eventually, 36 cases were included in this review, while cases without detailed clinical information or not reported in English were excluded from the analysis. To summarize, DFSP of the breast is an extremely rare malignancy characterized by spindle tumor cells arranged in a storiform pattern and positivity for CD34. The core needle biopsy is one of the crucial methods for its preoperative diagnosis. Management of DFSP is mainly based on surgical excision. It is prone to local recurrence, so long-term follow-up is required.
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http://dx.doi.org/10.1155/2020/8852182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671798PMC
April 2021

WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer.

Cell Death Dis 2020 11 21;11(11):1001. Epub 2020 Nov 21.

Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target therapeutically. Targeting synthetic lethality is an alternative approach for cancer treatment. TNBC shows frequent loss of phosphatase and tensin homologue (PTEN) expression, which is associated with poor prognosis and treatment response. To identify PTEN synthetic lethal interactions, TCGA analysis coupled with a whole-genome siRNA screen in isogenic PTEN-negative and -positive cells were performed. Among the candidate genes essential for the survival of PTEN-inactive TNBC cells, WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) expression was increased in the low vs. high PTEN TNBC samples. It was also the top hit in the siRNA screen and its knockdown significantly inhibited cell viability in PTEN-negative cells, which was further validated in 2D and 3D cultures. Mechanistically, WDHD1 is important to mediate a high demand of protein translation in PTEN-inactive TNBC. Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clinic-pathological information. Taken together, as an essential gene for the survival of PTEN-inactive TNBC cells, WDHD1 could be a potential biomarker or a therapeutic target for TNBC.
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http://dx.doi.org/10.1038/s41419-020-03210-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680459PMC
November 2020

white panicle2 encoding thioredoxin z, regulates plastid RNA editing by interacting with multiple organellar RNA editing factors in rice.

New Phytol 2021 03 19;229(5):2693-2706. Epub 2020 Dec 19.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

Thioredoxins (TRXs) occur in plant chloroplasts as complex disulphide oxidoreductases. Although many biological processes are regulated by thioredoxins, the regulatory mechanism of chloroplast TRXs are largely unknown. Here we report a rice white panicle2 mutant caused by a mutation in the thioredoxin z gene, an orthologue of AtTRX z in Arabidopsis. white panicle2 (wp2) seedlings exhibited a high-temperature-sensitive albinic phenotype. We found that plastid multiple organellar RNA editing factors (MORFs) were the regulatory targets of thioredoxin z. We showed that OsTRX z protein physically interacts with OsMORFs in a redox-dependent manner and that the redox state of a conserved cysteine in the MORF box is essential for MORF-MORF interactions. wp2 and OsTRX z knockout lines show reduced editing efficiencies in many plastidial-encoded genes especially under high-temperature conditions. An Arabidopsis trx z mutant also exhibited significantly reduced chloroplast RNA editing. Our combined results suggest that thioredoxin z regulates chloroplast RNA editing in plants by controlling the redox state of MORFs.
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http://dx.doi.org/10.1111/nph.17047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027827PMC
March 2021

Different Laboratory Abnormalities in COVID-19 Patients with Hypertension or Diabetes.

Virol Sin 2020 12 30;35(6):853-856. Epub 2020 Sep 30.

Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

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http://dx.doi.org/10.1007/s12250-020-00296-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524865PMC
December 2020

Stent retriever thrombectomy combined with long-term local thrombolysis for severe hemorrhagic cerebral venous sinus thrombosis.

Exp Ther Med 2020 Nov 9;20(5):66. Epub 2020 Sep 9.

Department of Neurosurgery, Qilu Hospital of Shandong University, Qingdao, Shandong 266035, P.R. China.

Cerebral venous sinus thrombosis (CVST) is a rare disease associated with high disability and mortality rates. A subset of patients do not respond to standard anticoagulation therapy, leading to the progression of CVST with hemorrhagic stroke, which represents a major challenge for its treatment. Severe hemorrhagic (SH)-CVST is life-threatening due to large hematoma, edema and/or cerebral hernia. Anticoagulation or thrombolytic therapy alone may lead to further aggravation of the hematoma. Stent retriever thrombectomy combined with long-term local thrombolysis (SRT-LLT) has been used in certain centers for those refractory cases or patients with new intracranial hemorrhage. However, to date, no studies on SRT-LLT treatment specifically for SH-CVST have been performed. The aim of the present retrospective study was to specifically evaluate the effectiveness of SRT-LLT in SH-CVST. Between December 2013 and November 2018, SRT-LLT was performed at our center in 8 patients with hemorrhagic CVST who did not respond to intravenous anticoagulation. The clinical characteristics, results of the radiological evaluation, details on the surgical procedure and clinical outcomes were assessed. The patients were administered systemic intravenous anticoagulation as the initial treatment following admission. SRT-LLT was performed when their condition deteriorated with a high risk of a fatal outcome within a short time period. SRT-LLT was performed in 8 patients, with successful recanalization confirmed by angiography. In 4 of the patients, complete recanalization was achieved, whereas in the remaining 4, recanalization was partial. There were no intraoperative complications. Two patients developed rebleeding after surgery, but they all gradually recovered. There were no treatment-associated fatalities. Therefore, SRT-LLT appears to be a feasible, safe and effective option for SH-CVST and it may be used as rescue therapy for carefully selected patients with SH-CVST.
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http://dx.doi.org/10.3892/etm.2020.9194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490800PMC
November 2020

The impact of anthelmintic treatment on gut bacterial and fungal communities in diagnosed parasite-free sika deer Cervus nippon.

Appl Microbiol Biotechnol 2020 Nov 15;104(21):9239-9250. Epub 2020 Sep 15.

College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

The gut microbiota, including both bacterial and fungal communities, plays vital roles in the gut homeostasis of animals, and antibiotics can lead to disorders of these microbial communities. The use of anthelmintic treatment to control parasitic infection has long been a standard practice, although its impact on the gut microbiota of healthy sika deer is relatively unknown. This study used next-generation sequencing based on 16S/18S/ITS rRNA genes to investigate the shifts in fecal bacterial and fungal communities in parasite-free sika deer after treatment with fenbendazole and ivermectin tablets. The α-diversity of both bacterial and fungal communities was significantly decreased (P < 0.05) after treatment, as were the bacterial genus Bacteroides and fungal genus Candida (P < 0.05). The results of β-diversity, LEfSe analysis, core community's analysis, taxonomic composition, and functional prediction of fungal and bacterial communities confirmed the substantial impacts of anthelmintic treatment on the function and structure of the intestinal microbiota of sika deer. Nevertheless, many lines of evidence, including β-diversity, LEfSe analysis and functional prediction analysis, suggested that the anthelmintics exerted more significant influences on fungal communities than on bacterial communities, suggesting that more attention should be paid to the changes in fungal communities of sika deer under anthelmintic treatment. The present study provides evidence to support the assumption that anthelmintic drugs modify the gut microbiota of deer and serves as the first trial to test the potential effects of anthelmintics on mycobiota in ruminants using high-throughput sequencing techniques. Key Points • Anthelmintic treatment showed significant effects on the gut microbiota of sika deer. • Fungi were more strongly affected by anthelmintic treatment than bacteria. • The profile of mycobiota provides essential data that were previously absent.
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http://dx.doi.org/10.1007/s00253-020-10838-yDOI Listing
November 2020

Miniaturization of the Superconducting Memory Cell a Three-Dimensional Nb Nano-superconducting Quantum Interference Device.

ACS Nano 2020 Sep 27;14(9):11002-11008. Epub 2020 Jul 27.

CAS Center for Excellence in Superconducting Electronics (CENSE), State Key Laboratory of Functional Material for Informatics, Shanghai Institute of Microsystem and Information Technology (SIMIT), Chinese Academy of Sciences (CAS), Shanghai 200050, China.

Scalable memories that can match the speeds of superconducting logic circuits have long been desired to enable a superconducting computer. A superconducting loop that includes a Josephson junction can store a flux quantum state in picoseconds. However, the requirement for the loop inductance to create a bistate hysteresis sets a limit on the minimal area occupied by a single memory cell. Here, we present a miniaturized superconducting memory cell based on a three-dimensional (3D) Nb nano-superconducting quantum interference device (nano-SQUID). The major cell area here fits within an 8 × 9 μm rectangle with a cross-selected function for memory implementation. The cell shows periodic tunable hysteresis between two neighboring flux quantum states produced by bias current sweeping because of the large modulation depth of the 3D nano-SQUID (∼66%). Furthermore, the measured current-phase relations (CPRs) of nano-SQUIDs are shown to be skewed from a sine function, as predicted by theoretical modeling. The skewness and the critical current of 3D nano-SQUIDs are linearly correlated. It is also found that the hysteresis loop size is in a linear scaling relationship with the CPR skewness using the statistics from characterization of 26 devices. We show that the CPR skewness range of π/4-3π/4 is equivalent to a large loop inductance in creating a stable bistate hysteresis for memory implementation. Therefore, the skewed CPR of 3D nano-SQUID enables further superconducting memory cell miniaturization by overcoming the inductance limitation of the loop area.
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http://dx.doi.org/10.1021/acsnano.0c04405DOI Listing
September 2020

Ultrasensitive electrochemiluminescent immunosensing based on trimetallic Au-Pd-Pt/MoS nanosheet as coreaction accelerator and self-enhanced ABEI-centric complex.

Anal Chim Acta 2020 Aug 28;1125:86-93. Epub 2020 May 28.

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

In this work, an ultrasensitive electrochemiluminescence (ECL) immunosensor for the determination of cystatin C (CYSC) was developed based on the combination of coreaction accelerator amplification and self-enhanced ECL luminophores. Trimetallic Au-Pd-Pt nanoflowers functionalized MoS nanosheet (Au-Pd-Pt/MoS) was used as an efficient coreaction accelerator of ABEI/O ECL system. Besides, the coreactant l-cysteine (L-Cys) was also cross-linked with ABEI to obtain self-enhanced ABEI-centric complex (ABEI-Cys) which was further immobilized onto the surface of Au-Pd-Pt/MoS nanosheet, thereby achieving an outstanding signal tagging. Benefiting from the coreaction accelerator amplification of Au-Pd-Pt/MoS nanosheet towards ABEI/O ECL system and efficient self-enhanced ABEI-Cys complex, this developed ECL immunosensor for CYSC detection exhibited a wide linear range from 1.0 fg/mL to 5.0 ng/mL with low limit of detection down to 0.35 fg/mL. More importantly, this proposed ECL immunosensing system could remain excellent feasibility in human serum, showing great potential application in clinical diagnosis for proteins monitoring.
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http://dx.doi.org/10.1016/j.aca.2020.05.055DOI Listing
August 2020

miR-24 Reduces Serum Lipid Levels and Inhibits Brain Tissue Cells Apoptosis of Rats with Cerebral Infarction.

Turk Neurosurg 2020 ;30(4):483-490

Qilu Hospital of Shandong University (Qingdao Campus), Department of Neurosurgery, Qingdao City, Shandong Province, China.

Aim: To study miR-24 effects on cerebral infarction in rats.

Material And Methods: A rat middle cerebral artery occlusion model (MCAO) was constructed. Intracerebroventricular stereotactic injection of miR-24 agomir/antagomir was performed in the rat MCAO model. According to different experiences, rats were divided into normal, sham, MCAO, miR-24 agomir and miR-24 antagomir groups. Serum TCH, HDL and TG levels were detected.

Results: Comparingthe normal and sham groups, we observed decreased relative miR-24 expression (p < 0.05) and increased cerebral infarction area percentage, apoptotic cells and relative caspase-3 protein expression (p < 0.05) in theMCAO, miR-24 agomirand miR-24 antagomir groups. TC, TG and HDL-C levels of the MCAO and miR-24 antagomir groups were higher than those of normal and sham groups (p < 0.05).Compared with the MCAO group, increased relative miR-24 expression (p < 0.05) and decreased TC, TG and HDL-C levels,cerebral infarction area percentage, number of apoptotic cells and caspase-3 expression (p < 0.05) were found in themiR-24 agomir group, contrasting with theobservations from the miR-24 antagomir group.

Conclusion: miR-24 reduced serum TCH, HDL and TG levels and inhibited brain tissue cell apoptosis in rats with cerebral infarction.
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http://dx.doi.org/10.5137/1019-5149.JTN.23127-18.2DOI Listing
November 2020

Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis.

Cell Death Discov 2020 30;6:54. Epub 2020 Jun 30.

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD UK.

Idiopathic pulmonary fibrosis (IPF) is a chronic scarring disease in which aging, environmental exposure(s) and genetic susceptibility have been implicated in disease pathogenesis, however, the causes and mechanisms of the progressive fibrotic cascade are still poorly understood. As epithelial-mesenchymal interactions are essential for normal wound healing, through human 2D and 3D in vitro studies, we tested the hypothesis that IPF fibroblasts (IPFFs) dysregulate alveolar epithelial homeostasis. Conditioned media from IPFFs exaggerated the wound-healing response of primary human Type II alveolar epithelial cells (AECs). Furthermore, AECs co-cultured with IPFFs exhibited irregular epithelialization compared with those co-cultured with control fibroblasts (NHLFs) or AECs alone, suggesting that epithelial homeostasis is dysregulated in IPF as a consequence of the abnormal secretory phenotype of IPFFs. Secretome analysis of IPFF conditioned media and functional studies identified the matricellular protein, SPARC, as a key mediator in the epithelial-mesenchymal paracrine signaling, with increased secretion of SPARC by IPFFs promoting persistent activation of alveolar epithelium via an integrin/focal adhesion/cellular-junction axis resulting in disruption of epithelial barrier integrity and increased macromolecular permeability. These findings suggest that in IPF fibroblast paracrine signaling promotes persistent alveolar epithelial activation, so preventing normal epithelial repair responses and restoration of tissue homeostasis. Furthermore, they identify SPARC-mediated paracrine signaling as a potential therapeutic target to promote the restoration of lung epithelial homoestasis in IPF patients.
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http://dx.doi.org/10.1038/s41420-020-0289-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327077PMC
June 2020

Changes of saliva microbiota in the onset and after the treatment of diabetes in patients with periodontitis.

Aging (Albany NY) 2020 07 7;12(13):13090-13114. Epub 2020 Jul 7.

Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.

The relationship between type 2 diabetes mellitus (T2DM) and oral microbiota is still insufficiently recognized. In the present study, we compared the salivary microbiome of nondiabetic individuals, treatment-naïve diabetic patients, and diabetic patients treated with metformin or a combination of insulin and other drugs. The α- and β-diversity demonstrated significant differences in the salivary microbiome between the nondiabetic people and patients with a history of diabetes, while little divergence was found among individuals with a history of diabetes. After characterizing the effects of periodontitis on the microbial composition of each group, the salivary microbiome of the treatment-naïve diabetic patient group was compared with that of nondiabetic people and the metformin/combined treatment groups. The results revealed changes in the contents of certain bacteria after both the onset and the treatment of diabetes; among these differential bacteria, varied in all processes. A subsequent correlational analysis of the differential bacteria and clinical characteristics demonstrated that salivary microbes were related to drug treatment and certain pathological changes. Finally, the four common differential bacteria were employed for distinguishing the treatment-naïve diabetic patients from the nondiabetic people and the treated patients, with prediction accuracies of 83.3%, 75% and 75%, respectively.
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http://dx.doi.org/10.18632/aging.103399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377876PMC
July 2020

Assessment of the Predictive Role of Serum Lipid Profiles in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

J Breast Cancer 2020 Jun 7;23(3):246-258. Epub 2020 May 7.

Department of Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Purpose: Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients.

Methods: A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles.

Results: Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup. According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, = 0.007) was an independent predictor of NAC efficacy.

Conclusion: High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients. These results are potentially considered beneficial in establishing treatment decisions.
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http://dx.doi.org/10.4048/jbc.2020.23.e32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311363PMC
June 2020

Temporal radiographic changes in COVID-19 patients: relationship to disease severity and viral clearance.

Sci Rep 2020 06 24;10(1):10263. Epub 2020 Jun 24.

Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

COVID-19 is "public enemy number one" and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 ), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman's Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.
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http://dx.doi.org/10.1038/s41598-020-66895-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314788PMC
June 2020

Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson's disease.

Sci Rep 2020 06 12;10(1):9521. Epub 2020 Jun 12.

Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong, China.

Catechol-O-methyltransferase (COMT) is one of the main enzymes in dopamine metabolism and is reported to be associated with susceptibility to Parkinson's disease (PD) and pharmacotherapy. However, researchers mostly focus on the most common polymorphism, rs4680. In this case-control study, we investigated the association of SNPs other than rs4680 with the levodopa (L-dopa) response and other clinical features in Chinese PD patients. Eleven single nucleotide polymorphisms (SNPs) in the COMT gene were genotyped, and clinical data were collected. Patients with the TT genotype of rs165728 or rs174699 had larger daily levodopa equivalent doses (LEDs) than the patients with CC and CT genotypes under the dominant model (p = 0.01421 for rs165728 and p = 0.02302 for rs174699). Under the dominant model, the patients with GG at rs4680 G > A had a lower occurrence of dyskinesia than those with AA and AG (p = 0.0196). Patients with CC at rs4633 had a lower occurrence of dyskinesia than those with TT and TC (p = 0.0429) under the dominant model. The frequencies of the rs174675 T and rs933271 C alleles were higher in PD patients than in the controls (p < 0.05). Our primary results showed the possible association of SNPs other than the most common functional rs4680 in COMT with interindividual variance in the L-dopa daily dose and susceptibility to dyskinesia in Chinese patients, although this was an exploratory study based on a small sample size. Larger and more randomized samples are necessary for further investigation.
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http://dx.doi.org/10.1038/s41598-020-65332-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293305PMC
June 2020