Publications by authors named "Yi Gao"

820 Publications

Influence of Lenslet Configuration on Short-Term Visual Performance in Myopia Control Spectacle Lenses.

Front Neurosci 2021 25;15:667329. Epub 2021 May 25.

Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China.

This study aimed to evaluate short-term visual performance and optical quality of three different lenslet configurations on myopia control spectacle lenses. This study utilized a cross-over design. Distance visual acuity (VA) was measured in 50 myopic children; contrast sensitivity (CS) was measured in 36 myopic children. For each test, four spectacle lenses were evaluated in a random order: single-vision lens (SVL), lens with concentric rings of highly aspherical lenslets (HAL), lens with concentric rings of slightly aspherical lenslets (SAL), and lens with honeycomb configuration of spherical lenslets (HC). The modulation transfer function (MTF) and MTF area (MTFa) were used to determine optical quality. All tests were performed monocularly on the right eye with full correction. HAL and SAL had larger MTFa than HC. VA in lenses with lenslets was significantly reduced compared to SVL (all < 0.01). The reduction in VA was worse with HC than with SAL ( = 0.02) and HAL ( = 0.03); no effect of lenslet asphericity was found ( > 0.05). VA changes induced by lenslets showed no correlation with spherical equivalent refraction (all > 0.05) and were weakly positively associated with age for SAL ( = 0.36, = 0.01) and HC ( = 0.31, = 0.03), but not for HAL ( = 0.30). The area under the log contrast sensitivity function (AULCSF) decreased with HAL and HC (all < 0.001) in all illumination levels, and AULCSF with HAL was higher than that with HC in a photopic condition (1.17 ± 0.10 vs. 1.10 ± 0.13, = 0.0004). The presence of lenslets did not affect CS at 3 cycles per degree (cpd) ( = 0.80). At 6 to 18 cpd, CS was significantly reduced by HAL and HC (all < 0.05), but not SAL ( > 0.05) compared to SVL. At high spatial frequencies (>12 cpd) both SAL and HAL reduced CS significantly less than HC (all < 0.01). Short-term visual performance was minimally impaired by looking through the lenslet structure of myopia control spectacle lenses. Concentric rings with aspherical lenslets had a significantly lower impact on both VA and CS than honeycomb configuration with spherical lenslets.
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http://dx.doi.org/10.3389/fnins.2021.667329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185291PMC
May 2021

Employing hypoxia characterization to predict tumour immune microenvironment, treatment sensitivity and prognosis in hepatocellular carcinoma.

Comput Struct Biotechnol J 2021 21;19:2775-2789. Epub 2021 Apr 21.

Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

The hypoxic microenvironment was recognized as a major driving force of the malignant phenotype in hepatocellular carcinoma (HCC), which contributes to tumour immune microenvironment (TIM) remodeling and tumor progression. Dysregulated hypoxia-related genes (HRGs) result in treatment resistance and poor prognosis by reshaping tumor cellular activities and metabolism. Approaches to identify the relationship between hypoxia and tumor progression provided new sight for improving tumor treatment and prognosis. But, few practical tools, forecasting relationship between hypoxia, TIM, treatment sensitivity and prognosis in HCC were reported. Here, we pooled mRNA transcriptome and clinical pathology data from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), and later developed a hypoxia risk model including four HRGs (). The high-risk group displayed poor clinical characteristics, a malignant phenotype with carcinogenesis/proliferation pathways activation () and immunosuppressive TIM (decreased immune cell infiltrations and upregulated immunosuppressive cytokines). Meanwhile, activated B cells, effector memory CD8 T cells and deregulation were associated with patient's survival, which might be the core changes of HCC hypoxia. Finally, we validated the ability of the hypoxia risk model to predict treatment sensitivity and found high hypoxia risk patients had poor responses to HCC treatment, including surgical resection, Sorafenib, Transarterial Chemoembolization (TACE) and immunotherapy. In conclusion, based on 4 HRGs, we developed and validated a hypoxia risk model to reflect pathological features, evaluate TIM landscape, predict treatment sensitivity and compounds specific to hypoxia signatures in HCC patients.
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http://dx.doi.org/10.1016/j.csbj.2021.03.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134035PMC
April 2021

A critical role of PvFtsH2 in the degradation of photodamaged D1 protein in common bean.

Hortic Res 2021 Jun 1;8(1):126. Epub 2021 Jun 1.

Key Laboratory of Soybean Molecular Design Breeding, Northeast Institute of Geography and Agroecology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Haping Road 138, Nangang District, 150081, Harbin City, Heilongjiang Province, China.

Light is required for initiating chloroplast biogenesis and photosynthesis; however, the photosystem II reaction center (PSII RC) can be photodamaged. In this study, we characterized pvsl1, a seedling-lethal mutant of Phaseolus vulgaris. This mutant showed lethality when exposed to sunlight irradiation and a yellow-green leaf phenotype when grown in a growth chamber under low-light conditions. We developed 124 insertion/deletion (INDEL) markers based on resequencing data of Dalong1 and PI60234, two local Chinese common bean cultivars, for genetic mapping. We identified Phvul.002G190900, which encodes the PvFtsH2 protein, as the candidate gene for this pvsl1 mutation through fine-mapping and functional analysis. A single-base deletion occurred in the coding region of Phvul.002G190900 in the pvsl1 mutant, resulting in a frameshift mutation and a truncated protein lacking the Zn metalloprotease domain. Suppressed expression of Phvul.002G190900 at the transcriptional level was detected, while no change in the subcellular localization signal was observed. The seedlings of pvsl1 exhibited hypersensitivity to photoinhibition stress. In the pvsl1 mutant, abnormal accumulation of the D1 protein indicated a failure to rapidly degrade damaged D1 protein in the PSII RC. The results of this study demonstrated that PvFtsH2 is critically required for survival and maintaining photosynthetic activity by degrading photodamaged PSII RC D1 protein in common bean.
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http://dx.doi.org/10.1038/s41438-021-00554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167180PMC
June 2021

MeCP2 drives hepatocellular carcinoma progression via enforcing HOXD3 promoter methylation and expression through the HB-EGF/EGFR pathway.

Mol Oncol 2021 May 24. Epub 2021 May 24.

Department of cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China.

Homeobox D3 (HOXD3), a member of the homeobox family, was described to regulate tumorigenesis, invasion, metastasis, and angiogenesis in various tumor types. However, the molecular mechanisms regulating HOXD3 during hepatocellular carcinoma (HCC) migration, invasion, and angiogenesis remain elusive. In this study, we demonstrated that HOXD3 expression is enhanced by the binding of methyl-CpG-binding protein 2 (MeCP2), a methyl-CpG binding protein, together with CREB1to the hypermethylated promoter of HOXD3. Inhibition of HOXD3 eliminated the tumorigenic effects of MeCP2 on HCC cells. Furthermore, HOXD3 directly targeted the promoter region of heparin-binding epidermal growth factor (HB-EGF) via the EGFR-ERK1/2 cell signaling pathway and promoted invasion, metastasis, and angiogenesis of HCC in vitro and in vivo. Additionally, elevated expression of MeCP2, CREB1, and HB-EGF in HCC correlated with a poor survival rate. Our findings reveal the function of the MeCP2/HOXD3/HB-EGF regulatory axis in HCC, rendering it an attractive candidate for the development of targeted therapeutics and as a potential biomarker in patients with HCC.
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http://dx.doi.org/10.1002/1878-0261.13019DOI Listing
May 2021

Genetic Variants, Circulating Level of MCP1 with Risk of Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Pharmgenomics Pers Med 2021 11;14:561-567. Epub 2021 May 11.

Respiratory Medicine, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, People's Republic of China.

Background: Chronic obstructive pulmonary disease (COPD) ranks one of the major causes of mortality worldwide. Inflammation is greatly involved in the pathogenesis of COPD. Monocyte chemoattractant protein-1 (MCP1) has been implicated to play an important role in the inflammatory response of various pathological processes.

Methods: In this study, we conducted a hospital-based case-control study in a Chinese population, aiming to evaluate the potential associations of genetic polymorphisms of the MCP1 gene (rs1024611, rs2857656, and rs4586) and circulating level of MCP1 with COPD risk.

Results: We found that rs1024611 (OR=1.37; 95% CI=1.11-1.69; -value=0.004) and rs4586 (OR=1.33; 95% CI=1.09-1.63; -value=0.006) were significantly associated with increased COPD risk. In the dominant model, both rs1024611 (OR=1.46; 95% CI=1.11-1.92; -value=0.006) and rs4586 (OR=1.56; 95% CI=1.18-2.07; -value=0.002) were significantly associated with increased COPD risk. Genotypes of rs1024611 and rs4586 with minor alleles had a significantly higher circulating level of MCP1 (<0.001). Meanwhile, a circulating level of MCP1 was significantly associated with increased COPD risk (OR for per quartile increment=1.35, 95% CI=1.21-1.52, <0.001).

Conclusion: Our study indicated that genetic polymorphisms of the MCP1 gene and circulating level of MCP1 contributed to the COPD risk in the Chinese population. MCP1 contributed importantly to the pathophysiological process and occurrence of COPD.
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http://dx.doi.org/10.2147/PGPM.S303799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124012PMC
May 2021

A simple lectin-based biochip might display the potential clinical value of glycomics in patients with spontaneous intracerebral hemorrhage.

Ann Transl Med 2021 Apr;9(7):544

Department of Pathology, Anhui Medical University, Hefei, China.

Background: Intracerebral hemorrhage (ICH) is a cerebrovascular disease with extremely high disability and mortality rates. Glycans play critical roles in biological processes. However, whether glycans can serve as potential biomarkers for determining clinical diagnosis and prognosis in ICH remains determined.

Methods: In this study, we established a lectin-biochip to measure serum glycans levels in ICH patients (n=48) and healthy controls (n=16). An enzyme-linked immunosorbent assay (ELISA) was carried out to determine serum levels of IL-10 and TNF-α in the patients. Correlation analyses of the serum glycan and cytokine levels and the clinicopathological parameters of patients were performed.

Results: The biochip-based data revealed that the serum levels of α-Man/α-Glc (ConA), Galβ3GalNAc (PNA), GalNAc (VVA), Fucα6GlcNAc (AAL), α-Fuc (LTL), and Galβ3GalNAc-Ser/Thr (AIL) significantly increased in the super-acute phase of ICH in comparison with healthy controls. Clinicopathological analysis indicated the serum levels of ConA, VVA, and LTL had significant associations with the National Institute of Health Stroke Scale (NIHSS), and serum VVA levels had a significant association with the Mini-Mental State Examination (MMSE) at day 90 after ICH. Correlation coefficient analysis revealed significant correlations between TNF-α and ConA (P<0.001) as well as between IL-10 and ConA (P<0.001), PNA (P=0.02), VVA (P<0.001), and MAL (P=0.04), respectively.

Conclusions: We established a proof-of-concept platform for detecting serum glycomics and highlighted their potential value in diagnosing and predicting ICH patients' outcomes.
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http://dx.doi.org/10.21037/atm-20-7315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105815PMC
April 2021

miR-5701 promoted apoptosis of clear cell renal cell carcinoma cells by targeting phosphodiesterase-1B.

Anticancer Drugs 2021 Apr 23. Epub 2021 Apr 23.

Department of Pathology, School of Basic Medical Sciences Institute of Genetics and Developmental Biology, Xi'an Jiaotong University Health Science Center Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an Jiaotong University Department of Pathology, The First Hospital of Xi'an Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Increasing evidence has demonstrated that microRNAs play critical roles in malignant biological behaviors, including cancerogenesis, cancer progression and metastasis, through the regulation of target genes expression. As miR-5701 has recently been identified to play roles as tumor suppressor miRNA in the development of some kinds of cancers, in this study we sought to investigate the role of miR-5701 in clear cell renal cell carcinoma (ccRCC). Colony formation, cell apoptosis and proliferation assays were employed, and the results showed that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells. Western blotting and dual-luciferase reporter assays were used to confirm that PDE1B is a new direct target of miR-5701. Furthermore, overexpression of PDE1B attenuated the effects of miR-5701, indicating that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells via targeting PDE1B. Taken together, the data presented here indicate that t miR-5701 is a tumor suppressor in ccRCC and PDE1B is a new target of miR-5701.
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http://dx.doi.org/10.1097/CAD.0000000000001078DOI Listing
April 2021

Development and Assessment of an Artificial Intelligence-Based Tool for Skin Condition Diagnosis by Primary Care Physicians and Nurse Practitioners in Teledermatology Practices.

JAMA Netw Open 2021 Apr 1;4(4):e217249. Epub 2021 Apr 1.

Google Health, Palo Alto, California.

Importance: Most dermatologic cases are initially evaluated by nondermatologists such as primary care physicians (PCPs) or nurse practitioners (NPs).

Objective: To evaluate an artificial intelligence (AI)-based tool that assists with diagnoses of dermatologic conditions.

Design, Setting, And Participants: This multiple-reader, multiple-case diagnostic study developed an AI-based tool and evaluated its utility. Primary care physicians and NPs retrospectively reviewed an enriched set of cases representing 120 different skin conditions. Randomization was used to ensure each clinician reviewed each case either with or without AI assistance; each clinician alternated between batches of 50 cases in each modality. The reviews occurred from February 21 to April 28, 2020. Data were analyzed from May 26, 2020, to January 27, 2021.

Exposures: An AI-based assistive tool for interpreting clinical images and associated medical history.

Main Outcomes And Measures: The primary analysis evaluated agreement with reference diagnoses provided by a panel of 3 dermatologists for PCPs and NPs. Secondary analyses included diagnostic accuracy for biopsy-confirmed cases, biopsy and referral rates, review time, and diagnostic confidence.

Results: Forty board-certified clinicians, including 20 PCPs (14 women [70.0%]; mean experience, 11.3 [range, 2-32] years) and 20 NPs (18 women [90.0%]; mean experience, 13.1 [range, 2-34] years) reviewed 1048 retrospective cases (672 female [64.2%]; median age, 43 [interquartile range, 30-56] years; 41 920 total reviews) from a teledermatology practice serving 11 sites and provided 0 to 5 differential diagnoses per case (mean [SD], 1.6 [0.7]). The PCPs were located across 12 states, and the NPs practiced in primary care without physician supervision across 9 states. The NPs had a mean of 13.1 (range, 2-34) years of experience and practiced in primary care without physician supervision across 9 states. Artificial intelligence assistance was significantly associated with higher agreement with reference diagnoses. For PCPs, the increase in diagnostic agreement was 10% (95% CI, 8%-11%; P < .001), from 48% to 58%; for NPs, the increase was 12% (95% CI, 10%-14%; P < .001), from 46% to 58%. In secondary analyses, agreement with biopsy-obtained diagnosis categories of maglignant, precancerous, or benign increased by 3% (95% CI, -1% to 7%) for PCPs and by 8% (95% CI, 3%-13%) for NPs. Rates of desire for biopsies decreased by 1% (95% CI, 0-3%) for PCPs and 2% (95% CI, 1%-3%) for NPs; the rate of desire for referrals decreased by 3% (95% CI, 1%-4%) for PCPs and NPs. Diagnostic agreement on cases not indicated for a dermatologist referral increased by 10% (95% CI, 8%-12%) for PCPs and 12% (95% CI, 10%-14%) for NPs, and median review time increased slightly by 5 (95% CI, 0-8) seconds for PCPs and 7 (95% CI, 5-10) seconds for NPs per case.

Conclusions And Relevance: Artificial intelligence assistance was associated with improved diagnoses by PCPs and NPs for 1 in every 8 to 10 cases, indicating potential for improving the quality of dermatologic care.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.7249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082316PMC
April 2021

Confidence interval estimation for sensitivity and difference between two sensitivities at a given specificity under tree ordering.

Authors:
Yi Gao Lili Tian

Stat Med 2021 Jul 27;40(16):3695-3723. Epub 2021 Apr 27.

Department of Biostatistics, University at Buffalo, Buffalo, New York, USA.

This article considers a setting in diagnostic studies (or biomarker study) which involves a healthy class and a diseased class and the latter consists of several subclasses. The problem of interest is to evaluate the accuracy of a biomarker (or a diagnostic test) measured on a continuous scale correctly identifying healthy subjects from diseased subjects without requiring specification of an ordering in terms of marker values for subclasses relative to each other within the diseased class. Such setting is quite common in practice and it falls in the framework of tree ordering or umbrella ordering. This article explores several parametric and nonparametric approaches for estimating confidence intervals of sensitivity of single biomarker and difference between sensitivities of two correlated biomarkers under tree ordering at a given specificity. The performances of all the methods are evaluated and compared by a comprehensive simulation study. A published microarray data set is analyzed using the proposed methods.
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http://dx.doi.org/10.1002/sim.8993DOI Listing
July 2021

Comparison of the Microsolvation of CaX (X = F, Cl, Br, I) in Water: Size-Selected Anion Photoelectron Spectroscopy and Theoretical Calculations.

J Phys Chem A 2021 Apr 19;125(16):3288-3306. Epub 2021 Apr 19.

Beijing National Laboratory for Molecular Sciences (BNLMS), State Key Laboratory of Molecular Reaction Dynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

To understand the microsolvation of alkaline-earth dihalides in water and provide information about the dependence of solvation processes on different halides, we investigated CaBr(HO), CaI(HO), and CaF(HO) ( = 0-6) clusters using size-selected anion photoelectron spectroscopy and conducted theoretical calculations on these clusters and their neutrals. The results are compared with those of CaCl(HO) clusters reported previously. It is found that the vertical detachment energies (VDEs) of CaCl(HO), CaBr(HO), and CaI(HO) show a similar trend with increasing cluster size, while the VDEs of CaF(HO) show a different trend. The VDEs of CaF(HO) are much lower than those of CaCl(HO), CaBr(HO), and CaI(HO). A detailed probing of the structures shows that a significant increase of the Ca-X distance (separation of Ca-X ion pair) in CaCl(HO), CaBr(HO), and CaI(HO) clusters occurred at about = 5. However, for CaF(HO), no abrupt change of the Ca-F distance with the increasing cluster size has been observed. In CaCl(HO), CaBr(HO), and CaI(HO), the Ca atom coordinates directly with 5 HO molecules. However, in CaF(HO), the Ca atom coordinates directly with only 2 or 3 HO molecules. The similarity or differences in the structures and coordination numbers are consistent with the fact that CaCl, CaBr, and CaI have similar solubility, while CaF has much lower solubility.
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http://dx.doi.org/10.1021/acs.jpca.1c00573DOI Listing
April 2021

The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats.

Front Cell Infect Microbiol 2021 2;11:640448. Epub 2021 Apr 2.

National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.
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http://dx.doi.org/10.3389/fcimb.2021.640448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050338PMC
April 2021

The combined induction of liver progenitor cells and the suppression of stellate cells by small molecules reverts chronic hepatic dysfunction.

Theranostics 2021 14;11(11):5539-5552. Epub 2021 Mar 14.

International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

We developed a cocktail of soluble molecules mimicking the milieu supporting liver regeneration that could convert mature hepatocytes to expandable liver progenitor-like cells . This study aimed to induce endogenous liver progenitor cells by the administration of the soluble molecules to provide an alternative approach for the resolution of liver fibrosis. cultured hepatocyte-derived liver progenitor-like cells (HepLPCs) were transplanted into CCL4-treated mice to investigate the therapeutic effect against liver fibrosis. Next, we used HGF in combination with a cocktail of small molecules (Y-27632, A-83-01, and CHIR99021 (HACY)) to induce endogenous CD24 liver progenitor cells and to inhibit the activation of hepatic stellate cells (HSCs) during CCL4-induced hepatic injury. RNA sequencing was performed to further clarify the features of HACY-induced CD24 cells compared with CCL4-induced CD24 cells and derived HepLPCs. Finally, we evaluated the expansion of HACY-induced CD24 cells in human hepatocyte-spheroids from fibrotic liver tissues. HepLPCs exhibited the capacity to alleviate liver fibrosis after transplantation into CCL4-treated mice. The administration of HACY not only induced the conversion of mature hepatocytes (MHs) to CD24 progenitor cells but prevented the activation of HSCs, thus leading to enhanced improvement of liver fibrosis in CCL4-treated mice. Compared to CD24 cells induced by CCL4 alone, HACY-induced CD24 cells retained an enhanced level of hepatic function and could promote the restoration of liver function that exhibited comparable gene expression profiles with HepLPCs. CD24 cells were also observed in human liver fibrotic tissues and were expanded in three-dimensional (3D) hepatic spheroids in the presence of HACY . Hepatocyte-derived liver progenitor-like cells are crucial for liver regeneration during chronic hepatic injuries. The administration of HACY, which allowed the induction of endogenous CD24 progenitor cells and the inactivation of HSCs, exerts beneficial effects in the treatment of liver fibrosis by re-establishing a balance favoring liver regeneration while preventing fibrotic responses.
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http://dx.doi.org/10.7150/thno.54457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039967PMC
March 2021

The preliminary evaluation of differential characteristics and factor evaluation of the microbial structure of rural household toilet excrement in China.

Environ Sci Pollut Res Int 2021 Apr 10. Epub 2021 Apr 10.

Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin, 300191, China.

Recent studies on the microbial community composition of human excrement after rural household toilet treatment are unclear regarding the effects and risks of using recycled products as fertilizers in agriculture. In this study, we used Illumina high-throughput sequencing to investigate the microbial community structure of the excrement from 50 Chinese rural household toilets on a spatial scale, and we evaluated the impact of select geochemical factors on the bacterial and fungal communities in the human excrement. Multivariate analysis showed that there was a significant spatial differentiation of the human excrement in microbial communities after all toilet treatments. Twenty dry toilet samples and thirty septic tank samples had similar bacterial (Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes) and fungal phyla (Ascomycota and Basidiomycota), differing only in the proportions of the microorganisms. For both dry toilet samples and septic tank samples, the pH and ammonium nitrogen were found to be the major driving forces affecting the changes in bacterial community structures (p<0.05), while there was no correlation found for the fungal community with environmental factors in China (p>0.05), except in the northern regions, where the total phosphorus was found to be significantly correlated with the fungal community (p<0.05). Network analysis confirmed that NH-N had the most significant impact on the content of pathogens. Certain pathogens were still detected after toilet treatment, such as Streptococcus, Bacteroides, Aspergillus, and Chrysosporium, and the proportion of potential pathogenic bacteria in dry toilets was higher than that in septic tanks, suggesting that septic tanks were better than dry toilets in treating human excrement. These results provide an ecological perspective for understanding the large-scale geographic distribution of household excrement microbial communities in rural areas and for improving human excrement treatment technologies and avoiding the risks of agricultural applications.
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http://dx.doi.org/10.1007/s11356-021-13779-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036012PMC
April 2021

Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous Deletion.

J Med Chem 2021 04 8;64(8):4430-4449. Epub 2021 Apr 8.

Agios Pharmaceuticals, Inc., 88 Sidney Street, Cambridge, Massachusetts 02139, United States.

The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was recently implicated as a synthetic lethal target in cancers with deletion of the methylthioadenosine phosphorylase () gene, which is adjacent to the tumor suppressor and codeleted with in approximately 15% of all cancers. Previous attempts to target MAT2A with small-molecule inhibitors identified cellular adaptations that blunted their efficacy. Here, we report the discovery of highly potent, selective, orally bioavailable MAT2A inhibitors that overcome these challenges. Fragment screening followed by iterative structure-guided design enabled >10 000-fold improvement in potency of a family of allosteric MAT2A inhibitors that are substrate noncompetitive and inhibit release of the product, -adenosyl methionine (SAM), from the enzyme's active site. We demonstrate that potent MAT2A inhibitors substantially reduce SAM levels in cancer cells and selectively block proliferation of -null cells both in tissue culture and xenograft tumors. These data supported progressing into current clinical studies (ClinicalTrials.gov NCT03435250).
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http://dx.doi.org/10.1021/acs.jmedchem.0c01895DOI Listing
April 2021

Enhancing the oxidative stability of algal oil emulsions by adding sweet orange oil: Effect of essential oil concentration.

Food Chem 2021 Sep 8;355:129508. Epub 2021 Mar 8.

State Key Laboratory of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, Jiangxi, China; National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.

The effects of sweet orange essential oil (SOEO) concentration (0-12.5% of oil phase) on the physical stability, oxidative stability, and interfacial composition of algal oil-in-water emulsions containing sodium caseinate-coated oil droplets was examined. SOEO addition had no influence on the microstructure and physical stability of the algal oil emulsions. The addition of SOEO enhanced the oxidation stability of algal oil emulsion. As an example, the values of algal oil emulsions with 0 and 10% SOEO were 198 and 100 mmol/kg algal oil after 16 days of accelerated oxidation, respectively. The absorbed protein level was higher in the algal oil emulsion containing 10% SOEO (70%) than in 0% SOEO (57%). This result suggested that the presence of SOEO enhanced the interfacial thickness, possibly by interacting with the casein molecules. A thicker protein layer may have helped to retard the oxidation of the omega-3 oils inside lipid droplets.
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http://dx.doi.org/10.1016/j.foodchem.2021.129508DOI Listing
September 2021

Genome-wide Expression Analysis Identifies the Association between SEC14L2 and Castration-resistant Prostate Cancer Survival.

J Cancer 2021 22;12(8):2173-2180. Epub 2021 Feb 22.

Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Mechanism of castration-resistant prostate cancer (CRPC) is still unclear. Our objective is to investigate the association between genes expression and CRPC through the genome-wide approach and functional researches. Differentially expressed genes (DEGs) between PCa and CRPC tissues were identified using expression profile obtained from Gene Expression Omnibus database (GEO). Survival analysis was performed using online database Gene Expression Profiling Interactive Analysis (GEPIA). Oncomine database was further used to explore the relationship between DEGs expression levels with clinical parameters. After study, SEC14L2-knockdown CRPC cells and normal prostatic epithelial cells were used for study to verify its biological functions. A total of 3 consistently changed DEGs (SEC14L2, DMD, SEL1L) were identified correlating with CRPC after cross validation in three independent datasets. Low expression of SEC14L2 was associated with poorer disease-free survival and higher Gleason score than normal/high expression of SEC14L2. SEC14L2 knockdown promoted cell proliferation, migration, invasion as well as cell cycle progression in CRPC cells (all P<0.05) while no significant effects were observed in normal prostatic epithelial cells. Low expression of SEC14L2 was significantly associated with CRPC, and correlated with PCa aggressiveness and poorer prognosis. SEC14L2 might be a potential biomarker or drug target for CRPC.
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http://dx.doi.org/10.7150/jca.50299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974876PMC
February 2021

Single-atom alloy catalysts designed by first-principles calculations and artificial intelligence.

Nat Commun 2021 Mar 23;12(1):1833. Epub 2021 Mar 23.

Center for Energy Science and Technology, Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Moscow, Russia.

Single-atom-alloy catalysts (SAACs) have recently become a frontier in catalysis research. Simultaneous optimization of reactants' facile dissociation and a balanced strength of intermediates' binding make them highly efficient catalysts for several industrially important reactions. However, discovery of new SAACs is hindered by lack of fast yet reliable prediction of catalytic properties of the large number of candidates. We address this problem by applying a compressed-sensing data-analytics approach parameterized with density-functional inputs. Besides consistently predicting efficiency of the experimentally studied SAACs, we identify more than 200 yet unreported promising candidates. Some of these candidates are more stable and efficient than the reported ones. We have also introduced a novel approach to a qualitative analysis of complex symbolic regression models based on the data-mining method subgroup discovery. Our study demonstrates the importance of data analytics for avoiding bias in catalysis design, and provides a recipe for finding best SAACs for various applications.
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http://dx.doi.org/10.1038/s41467-021-22048-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988173PMC
March 2021

Deep reinforcement learning of transition states.

Phys Chem Chem Phys 2021 Mar 17;23(11):6888-6895. Epub 2021 Mar 17.

Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, 518055 Shenzhen, China.

Combining reinforcement learning (RL) and molecular dynamics (MD) simulations, we propose a machine-learning approach, called RL, to automatically unravel chemical reaction mechanisms. In RL, locating the transition state of a chemical reaction is formulated as a game, and two functions are optimized, one for value estimation and the other for policy making, to iteratively improve our chance of winning this game. Both functions can be approximated by deep neural networks. By virtue of RL, one can directly interpret the reaction mechanism according to the value function. Meanwhile, the policy function allows efficient sampling of the transition path ensemble, which can be further used to analyze reaction dynamics and kinetics. Through multiple experiments, we show that RL can be trained tabula rasa hence allowing us to reveal chemical reaction mechanisms with minimal subjective biases.
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http://dx.doi.org/10.1039/d0cp06184kDOI Listing
March 2021

Rapid rotational magneto-acousto-electrical tomography with filtered back-projection algorithm based on plane waves.

Phys Med Biol 2021 Apr 21;66(9). Epub 2021 Apr 21.

School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.

Magneto-acousto-electrical tomography (MAET) is designed to produce conductivity images with high spatial resolution for a conducting object. In a previous study, for an irregular conductor, transverse scanning and rotational methods with a focus transducer were combined to collect complete electrical information. This kind of method, however, is time-consuming because of the transverse scanning procedure. In this study, we proposed a novel imaging method based on plane ultrasound waves and a new aspect of projection in rotational MAET. In the proposed method, we achieved the projection in each rotation angle by using plane waves rather than mechanical scanning of the focus waves along the transverse direction. Thus, the imaging time was significantly saved. To verify the proposed method, we derived a measurement formula containing a lateral integration, which built the relationship between the measurement formula and the projection under each rotation angle. Next, we constructed two different numerical models to compute magneto-acousto-electrical signals by using a finite element method and reconstructed the corresponding conductivity parameter images based on a filtered back-projection algorithm. Then, simulated signals under different signal-to-ratios (6, 20, 40, and 60 dB) were generated to test the performance of the proposed algorithm. To improve the image quality, we further analysed the influence of the filters and the frequency scaling factors embedded in the filtered back-projection algorithm. Moreover, we computed the Lnorm of the error in case of different frequency scaling factors and measurement noises. Finally, we conducted a phantom experiment with a 64-element linear phased array transducer (center frequency of 2.7 MHz) and reconstructed the conductivity parameter images of the circular phantom with an elliptical hole. The experimental results demonstrated the feasibility and time-efficiency of the proposed rapid rotational MAET.
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http://dx.doi.org/10.1088/1361-6560/abef43DOI Listing
April 2021

[The effect of parisib on chondrocytes in osteoarthritis rats].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Nov;36(6):652-655

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http://dx.doi.org/10.12047/j.cjap.6024.2020.136DOI Listing
November 2020

Development and validation of a risk stratification model for predicting the mortality of acute kidney injury in critical care patients.

Ann Transl Med 2021 Feb;9(4):323

School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China.

Background: This study aimed to develop and validate a model for mortality risk stratification of intensive care unit (ICU) patients with acute kidney injury (AKI) using the machine learning technique.

Methods: Eligible data were extracted from the Medical Information Mart for Intensive Care (MIMIC-III) database. Calibration, discrimination, and risk classification for mortality prediction were evaluated using conventional scoring systems and the new algorithm. A 10-fold cross-validation was performed. The predictive models were externally validated using the eICU database and also patients treated at the Second People's Hospital of Shenzhen between January 2015 to October 2018.

Results: For the new model, the areas under the receiver operating characteristic curves (AUROCs) for mortality during hospitalization and at 28 and 90 days after discharge were 0.91, 0.87, and 0.87, respectively, which were higher than for the Simplified Acute Physiology Score (SAPS II) and Sequential Organ Failure Assessment (SOFA). For external validation, the AUROC was 0.82 for in-hospital mortality, higher than SOFA, SAPS II, and Acute Physiology and Chronic Health Evaluation (APACHE) IV in the eICU database, but for the 28- and 90-day mortality, the new model had AUROCs (0.79 and 0.80, respectively) similar to that of SAPS II in the SZ2 database. The reclassification indexes were superior for the new model compared with the conventional scoring systems.

Conclusions: The new risk stratification model shows high performance in predicting mortality in ICU patients with AKI.
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http://dx.doi.org/10.21037/atm-20-5723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944298PMC
February 2021

Tumour extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumour cells.

J Extracell Vesicles 2020 Nov 28;10(1):e12031. Epub 2020 Nov 28.

Department of Pathology, Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong.

The complement system is involved in the immunosurveillance of pathogens and tumour cells. Proteomic profiling revealed that extracellular vesicles (EVs) released by metastatic hepatocellular carcinoma (HCC) cells contained a significant number of complement proteins. Complement Factor H (CFH), an abundant soluble serum protein that inhibits the alternative complement pathway, was found to be highly expressed in EVs of metastatic HCC cell lines. Here, we investigated the functional role of EV-CFH and explored the therapeutic efficacy of targeting EV-CFH with an anti-CFH antibody in HCC. The results showed that EVs that are enriched in CFH promoted HCC cell growth, migration, invasiveness and enhanced liver tumour formation in mice. EV-CFH also promoted metastasis, which was significantly abrogated when treated with an anti-CFH antibody. These findings demonstrate an unexplored function of EV-CFH in protecting HCC cells by evading complement attack, thereby facilitating tumorigenesis and metastasis. Lastly, we demonstrated the therapeutic efficacy of an anti-CFH antibody in suppressing tumour formation in a syngeneic mouse model. This study suggests a new therapeutic strategy for HCC, by inhibiting EV-CFH with a tumour specific anti-CFH antibody.
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http://dx.doi.org/10.1002/jev2.12031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890557PMC
November 2020

In situ identification of the metallic state of Ag nanoclusters in oxidative dispersion.

Nat Commun 2021 Mar 3;12(1):1406. Epub 2021 Mar 3.

State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, China.

Oxidative dispersion has been widely used in regeneration of sintered metal catalysts and fabrication of single atom catalysts, which is attributed to an oxidation-induced dispersion mechanism. However, the interplay of gas-metal-support interaction in the dispersion processes, especially the gas-metal interaction has not been well illustrated. Here, we show dynamic dispersion of silver nanostructures on silicon nitride surface under reducing/oxidizing conditions and during carbon monoxide oxidation reaction. Utilizing environmental scanning (transmission) electron microscopy and near-ambient pressure photoelectron spectroscopy/photoemission electron microscopy, we unravel a new adsorption-induced dispersion mechanism in such a typical oxidative dispersion process. The strong gas-metal interaction achieved by chemisorption of oxygen on nearly-metallic silver nanoclusters is the internal driving force for dispersion. In situ observations show that the dispersed nearly-metallic silver nanoclusters are oxidized upon cooling in oxygen atmosphere, which could mislead to the understanding of oxidation-induced dispersion. We further understand the oxidative dispersion mechanism from the view of dynamic equilibrium taking temperature and gas pressure into account, which should be applied to many other metals such as gold, copper, palladium, etc. and other reaction conditions.
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http://dx.doi.org/10.1038/s41467-021-21552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930130PMC
March 2021

Comparison of Efficacy of Teriparatide (Parathyroid Hormone 1-34) Alone and in Combination with Zoledronic Acid for Osteoporosis in Postmenopausal Women.

J Coll Physicians Surg Pak 2021 Feb;31(2):240-242

Department of Orthopedics and Traumatology, First Clinical Medical College, Nanjing University of Chinese Medicine, China.

The purpose of this study was to compare the efficacy of teriparatide (parathyroid hormone 1-34) alone and in combination with zoledronic acid (ZA) for the treatment of osteoporosis in postmenopausal women. Ninety-six patients were randomly equally divided into Groups A (n=48) and B (n=48). Group A was given parathyroid hormone 1-34 alone. Group B was treated with parathyroid hormone 1-34 plus ZA. Visual analogue scale (VAS) score, bone mineral density(BMD), serum osteopontin (OPN), and C-terminal cross-linking telopeptide of type I collagen (S-CTX) etc. were compared. After 6 months of treatment, VAS score, serum OPN and S-CTX levels in Group B were significantly lower than those in Group A (p=0.001, p<0.001 and p<0.001, respectively); and BMD values of lumbar vertebrae L2-4, femoral neck and total hip bone in Group B were higher than those of Group A (p=0.002, p=0.028 and p<0.001, respectively). In conclusion, parathyroid hormone 1-34 plus ZA is more effective than parathyroid hormone 1-34 alone in treating post postmenopausal osteoporosis. Key Words: Teriparatide (parathyroid hormone 1-34, Zoledronic acid (ZA), Postmenopausal, Osteoporosis, Bone mineral density (BMD).
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http://dx.doi.org/10.29271/jcpsp.2021.02.240DOI Listing
February 2021

Structure reconstruction of metal/alloy in reaction conditions: a volcano curve?

Faraday Discuss 2021 May 26;229:62-74. Epub 2021 Feb 26.

Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China and Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

Recent in situ works have shown extensive evidence of the dramatic and reversible structure reconstructions of metal and alloy materials in reaction conditions. The reconstructions are of primary interest because they could lead to alternative catalytic mechanisms during real reactions. However, how the catalyst structure evolves under the pressures relevant to industrial applications (>1 atm) is so far unexplored. In our recent works, we have developed multiscale theoretical models to give reliable and precise predictions of the equilibrium shapes of metal nanoparticles and of the segregation properties of alloy surfaces at a given temperature and gas pressure. The theoretical predictions have been successfully used in interoperations of various in situ experimental observations. In this work, we applied these methods to study the detailed structural information of metal NPs and of bimetallic alloys at the temperature from 300 to 1000 K and the gas pressure from 10 to 10 Pa. The results show, in some cases, both the gas-induced shape change and the gas-induced segregation change are maximized when the gas adsorption is 'just right'. The fraction of the low-coordinated sites of the metal NP shows a volcano-like curve with pressure at a constant temperature. A similar volcano shape could also be found in the plot of the environmental segregation energy as functions of temperature and pressure. The similar gas effects at low pressure and at high pressure indicate the structural information obtained in laboratory environments (<1 atm) could be of use to understanding the catalysts structure reconstruction in industrial conditions (>1 atm).
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http://dx.doi.org/10.1039/c9fd00128jDOI Listing
May 2021

Robust expansion and functional maturation of human hepatoblasts by chemical strategy.

Stem Cell Res Ther 2021 Feb 25;12(1):151. Epub 2021 Feb 25.

Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou, 510530, China.

Background: Chemically strategies to generate hepatic cells from human pluripotent stem cells (hPSCs) for the potential clinical application have been improved. However, producing high quality and large quantities of hepatic cells remain challenging, especially in terms of step-wise efficacy and cost-effective production requires more improvements.

Methods: Here, we systematically evaluated chemical compounds for hepatoblast (HB) expansion and maturation to establish a robust, cost-effective, and reproducible methodology for self-renewal HBs and functional hepatocyte-like cell (HLC) production.

Results: The established chemical cocktail could enable HBs to proliferate nearly 3000 folds within 3 weeks with preserved bipotency. Moreover, those expanded HBs could be further efficiently differentiated into homogenous HLCs which displayed typical morphologic features and functionality as mature hepatocytes including hepatocyte identity marker expression and key functional activities such as cytochrome P450 metabolism activities and urea secretion. Importantly, the transplanted HBs in the injured liver of immune-defect mice differentiated as hepatocytes, engraft, and repopulate in the injured loci of the recipient liver.

Conclusion: Together, this chemical compound-based HLC generation method presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery application.
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http://dx.doi.org/10.1186/s13287-021-02233-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908723PMC
February 2021

Cross-modal motion aftereffects transfer between vision and touch in early deaf adults.

Sci Rep 2021 Feb 23;11(1):4395. Epub 2021 Feb 23.

Department of Psychology, University of Nevada, Reno, NV, 89557-0296, USA.

Previous research on early deafness has primarily focused on the behavioral and neural changes in the intact visual and tactile modalities. However, how early deafness changes the interplay of these two modalities is not well understood. In the current study, we investigated the effect of auditory deprivation on visuo-tactile interaction by measuring the cross-modal motion aftereffect. Consistent with previous findings, motion aftereffect transferred between vision and touch in a bidirectional manner in hearing participants. However, for deaf participants, the cross-modal transfer occurred only in the tactile-to-visual direction but not in the visual-to-tactile direction. This unidirectional cross-modal motion aftereffect found in the deaf participants could not be explained by unisensory motion aftereffect or discrimination threshold. The results suggest a reduced visual influence on tactile motion perception in early deaf individuals.
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http://dx.doi.org/10.1038/s41598-021-83960-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902672PMC
February 2021

Predicting Non-Alcoholic Fatty Liver Disease Progression and Immune Deregulations by Specific Gene Expression Patterns.

Front Immunol 2020 26;11:609900. Epub 2021 Jan 26.

Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, China.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide with rising rates in parallel to obesity, type 2 diabetes, and metabolic syndrome. NAFLD includes pathologies ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis and cirrhosis (NASH), which may eventually develop into hepatocellular carcinoma (HCC). Mechanically, lipids accumulation and insulin resistance act as the first hit, inflammation and fibrosis serve as the second hit. Currently, the diagnosis of NAFLD mainly depends on pathology examination and medical imaging, whereas proper gene signature classifiers are necessary for the evaluation of disease status. Here, we developed three signature classifiers to distinguish different NAFLD disease states (NAFL and NASH). Moreover, we found that B cells, DCs, and MAIT cells are key deregulated immune cells in NAFLD, which are associated with NAFLD and NAFLD-HCC progression. Meanwhile, AKR1B10 and SPP1 are closely related to the above three immune cell infiltrations and immunosuppressive cytokines expressions in NAFLD and NAFLD-HCC. Subsequently, we screened out AKR1B10 and SPP1 sensitive molecules TGX-221, which may provide a possible therapy for NAFLD and NAFLD-HCC.
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http://dx.doi.org/10.3389/fimmu.2020.609900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870871PMC
January 2021

Simple sequence repeats drive genome plasticity and promote adaptive evolution in penaeid shrimp.

Commun Biol 2021 Feb 11;4(1):186. Epub 2021 Feb 11.

CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

Simple sequence repeats (SSRs) are rare (approximately 1%) in most genomes and are generally considered to have no function. However, penaeid shrimp genomes have a high proportion of SSRs (>23%), raising the question of whether these SSRs play important functional and evolutionary roles in these SSR-rich species. Here, we show that SSRs drive genome plasticity and adaptive evolution in two penaeid shrimp species, Fenneropenaeus chinensis and Litopenaeus vannamei. Assembly and comparison of genomes of these two shrimp species at the chromosome-level revealed that transposable elements serve as carriers for SSR expansion, which is still occurring. The remarkable genome plasticity identified herein might have been shaped by significant SSR expansions. SSRs were also found to regulate gene expression by multi-omics analyses, and be responsible for driving adaptive evolution, such as the variable osmoregulatory capacities of these shrimp under low-salinity stress. These data provide strong evidence that SSRs are an important driver of the adaptive evolution in penaeid shrimp.
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http://dx.doi.org/10.1038/s42003-021-01716-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878876PMC
February 2021

A DNA Sequence Based Polymer Model for Chromatin Folding.

Authors:
Rui Zhou Yi Qin Gao

Int J Mol Sci 2021 Jan 29;22(3). Epub 2021 Jan 29.

Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.

The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further divided into spatially segregated compartments (A and B). The compartment B tends to be located near to the periphery or the nuclear center and interacts with other domains of compartments B, while compartment A tends to be located between compartment B and interacts inside the domains. These spatial domains are found to highly correlate with the mosaic CpG island (CGI) density. High CGI density corresponds to compartments A and small TADs, and vice versa. The variation of contact probability as a function of sequential distance roughly follows a power-law decay. Different chromosomes tend to segregate to occupy different chromosome territories. A model that can integrate these properties at multiple length scales and match many aspects is highly desired. Here, we report a DNA-sequence based coarse-grained block copolymer model that considers different interactions between blocks of different CGI density, interactions of TAD formation, as well as interactions between chromatin and the nuclear envelope. This model captures the various single-chromosome properties and partially reproduces the formation of chromosome territories.
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http://dx.doi.org/10.3390/ijms22031328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865792PMC
January 2021