Publications by authors named "Xiao Zhu"

498 Publications

The complete chloroplast genome of (Poaceae: ) and phylogenetic analysis.

Mitochondrial DNA B Resour 2021 Apr 1;6(4):1285-1286. Epub 2021 Apr 1.

Bamboo Research Institute, Guizhou University, Guiyang, China.

is a kind of bamboo that has excellent edible and economic value, which is endemic to southwest China. The study used next-generation sequencing to obtain the complete chloroplast (cp) genome sequence of . The cp genome of has a total length of 138,908 bp, and consisted of an 82,495-bp large single-copy region, an 12,743-bp small single-copy region, and two 21,835-bp IR regions. In total, 112 unique genes were found in the cp genome, including 77 protein coding, 31 tRNA, and 4 rRNA genes. Phylogenetic analysis indicated that and are sister species within the genus, where and are more closely related to them.
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http://dx.doi.org/10.1080/23802359.2021.1886007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018436PMC
April 2021

Clinical and Prognostic Pan-Cancer Analysis of N6-Methyladenosine Regulators in Two Types of Hematological Malignancies: A Retrospective Study Based on TCGA and GTEx Databases.

Front Oncol 2021 18;11:623170. Epub 2021 Mar 18.

The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang, China.

N6-methyladenosine (m6A) is one of the most active modification factors of mRNA, which is closely related to cell proliferation, differentiation, and tumor development. Here, we explored the relationship between the pathogenesis of hematological malignancies and the clinicopathologic parameters. The datasets of hematological malignancies and controls were obtained from the TCGA [AML (n = 200), DLBCL (n = 48)] and GTEx [whole blood (n = 337), blood vascular artery (n = 606)]. We analyzed the m6A factor expression differences in normal tissue and tumor tissue and their correlations, clustered the express obvious clinical tumor subtypes, determined the tumor risk score, established Cox regression model, performed univariate and multivariate analysis on all datasets. We found that the AML patients with high expression of IGF2BP3, ALKBH5, and IGF2BP2 had poor survival, while the DLBCL patients with high expression of METTL14 had poor survival. In addition, "Total" datasets analysis revealed that IGF2BP1, ALKBH5, IGF2BP2, RBM15, METTL3, and ZNF217 were potential oncogenes for hematologic system tumors. Collectively, the expressions of some m6A regulators are closely related to the occurrence and development of hematologic system tumors, and the intervention of specific regulatory factors may lead to a breakthrough in the treatment in the future.
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http://dx.doi.org/10.3389/fonc.2021.623170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015800PMC
March 2021

Predictive Analysis of the Neutralization Activity in Convalescent Plasmas From COVID-19 Recovered Patients in Zhejiang Province, China, January-March, 2020.

Front Cell Infect Microbiol 2021 16;11:650487. Epub 2021 Mar 16.

Institute of Parasitic Diseases, Hangzhou Medical College, Hangzhou, China.

Background: Convalescent plasma (CP) transfusion is considered to be the priority therapeutic option for COVID-19 inpatients when no specific drugs are available for emerging infections. An alternative, simple, and sensitive method is urgently needed for clinical use to detect neutralization activity of the CP to avoid the use of inconvenient micro-neutralization assay.

Method: This study aims to explore optimal index in predicting the COVID-19 CP neutralization activity (neutralizing antibody titers, NAb titers) in an indirect ELISA format. Fifty-seven COVID-19-recovered patients plasma samples were subjected to anti-SARS-CoV-2 RBD, S1, and N protein IgG antibody by indirect ELISA.

Results: ELISA-RBD exhibited high specificity (96.2%) and ELISA-N had high sensitivity (100%); while ELISA-S1 had low sensitivity (86.0%) and specificity (73.1%). Furthermore, ELISA-RBD IgG titers and pseudovirus-based NAb titers correlated significantly, with R of 0.2564 (P < 0.0001).

Conclusion: ELISA-RBD could be a substitute for the neutralization assay in resource-limited situations to screen potential plasma donors for further plasma infusion therapy.
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http://dx.doi.org/10.3389/fcimb.2021.650487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008148PMC
April 2021

Association Between Regulatory Emotional Self-Efficacy and Immunosuppressive Medication Adherence in Renal Transplant Recipients:Does Medication Belief Act as a Mediator?

Front Pharmacol 2021 8;12:559368. Epub 2021 Mar 8.

Nursing Department, Third Xiangya Hospital, Central South University, Changsha, China.

Few studies have investigated the association between regulatory emotional self-efficacy (RESE) and immunosuppressive medication adherence or the mechanisms underlying this relationship. Considering that previous evidence of immunosuppressive medication adherence depended on the level of immunosuppressive medication beliefs, a model of multiple mediation was tested in which immunosuppressive medication beliefs acted as mediators of the relationship between RESE and immunosuppressive medication adherence. A retrospective cross-sectional study was performed in 293 renal transplant patients during outpatient follow-ups from November 2019 to February 2020 in China. All participants completed a general demographic questionnaire, the Chinese version of the RESE, the Beliefs about Medication Questionnaire, and the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS). Spearson correlation analysis was carried out to identify the correlation between RESE and immunosuppressive medication adherence. Binary logistic regression analysis was performed to confirm factors associated with immunosuppressive medication adherence in renal transplant recipients. Mediating effect analysis was used to explore the internal interaction between RESE and immunosuppressive medication adherence. A total of 293 renal transplant patients were recruited, including 111 women and 182 men with a mean age of 42.5 years (SD = 10.0). A total of 23.21% of patients exhibited immunosuppressive medication none-adherence behavior, and 12.97% reported altering the prescribed amount of immunosuppressive medication without physician permission, which was most popular behavior among patients. The mean RESE score was 45.78 ± 6.12; the positive (POS) score was the highest, and the anger-irritation (ANG) score was the lowest. The correlation analysis results showed that RESE ( = -0.642, < 0.01) and immunosuppressive medication beliefs ( = -0.534, 0.01) were significantly associated with immunosuppressive medication adherence. Binary logistic regression analysis indicated that marital status, fertility status, rejection, immunosuppressive medication beliefs, and RESE were found to be independent predictors of immunosuppressive medication adherence [ = 0.803, < 0.05]. The results of the mediating effect analysis showed that immunosuppressive medication necessity had a partial mediating effect, RESE directly and indirectly affected immunosuppressive medication adherence via immunosuppressive medication necessity, and immunosuppressive medication concerns were not a mediator between RESE and immunosuppressive medication adherence. The levels of immunosuppressive medication adherence in renal transplant patients need to be improved in China. Marital status, fertility status, rejection, immunosuppressive medication beliefs, and RESE were major factors affecting immunosuppressive medication adherence. RESE could affect immunosuppressive medication adherence indirectly through immunosuppressive medication necessity.
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http://dx.doi.org/10.3389/fphar.2021.559368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982474PMC
March 2021

First report of chili pepper fruit rot caused by Fusarium incarnatum in China.

Plant Dis 2021 Mar 23. Epub 2021 Mar 23.

Shangqiu Normal University, Shangqiu 476000, Henan, P.R. ChinaShangqiu, China, 476000;

Pepper (Capsicum annuum L.), with annual production over 1 million tons, is ranked the first vegetable crop in Hainan Province, China. In December 2018, fruit rot of chili pepper , with yield loss of up to 15%, was found in 10 fields (12 hm2) in Yacheng (18°N, 109°E), Hainan Province, China. Water-soaked and soft lesions developed on fruit, with white to light gray fungal mycelium present inside. The diseased fruit turned soft and decayed at the later stages. Diseased tissue was cut into 12 pieces of 0.5×0.5 cm, surface-disinfected with 2% sodium hypochlorite for 2 min, followed by 70% ethanol for 30 s, rinsed with sterile distilled water five times, and plated onto potato dextrose agar (PDA). After growing on PDA for 2 to 3 days at 28°C in an incubator without light, 10 pure culture isolates were obtained. All isolates had abundant dense white aerial mycelia that became beige with age. The macroconidia were slightly curved with four to seven septa, 29.51 to 42.15 × 4.29 to 6.22 μm. Spindle-shaped mesoconidia with three to four septa were abundantly produced, 20.34 to 24.54 × 4.58 to to 11.70 × 2.35 to 3.20 μm. Chlamydospores were absent. Based on the morphological characteristics, the fungus was tentatively identified as Fusarium incarnatum (Leslie and Summerell 2006). An isolate SQHP-01 was chosen for molecular identification and pathogenicity test. Two DNA fragments of the isolate, the internal transcribed spacer (ITS) and translation elongation factor genes (EF-1α) were amplified for sequencing. BLAST analysis showed that sequences of ITS (GenBank acc. no. MN317371) and EF-1α (acc. No. MN928788) had 99.61 to 100% identity with those of known F. incarnatum (MN480497 and KF993969). Phylogenetic analysis was conducted using neighbor-joining algorithm based on ITS and EF-1a genes separately, and the isolate was well clustered with F. incarnatum both with 100% bootstrap support. Pathogenicity test of the isolate were carried out twice on five healthy chili pepper fruit. After surface-disinfection, fruit were wounded at three different points and 20 μl of conidial suspension (106 conidia/ml) were deposited on each wound. Unwounded inoculation was conducted by spreading 100 μl of the suspension on each fruit surface including the pedicel and calyx. The fruit spread with sterile distilled water represented the negative control. All fruit treatments were placed on the moist sterile cotton in moist chambers at 25°C with 16 h light and 8 h darkness. After 4 to 6 days, water-soaked necrotic lesions appeared on the wounded fruit, the symptoms identical to those observed in the field. Water-soaked necrotic lesions developed on the pedicel and calyx of unwounded fruit. No symptoms were observed on the control fruit. The morphology and sequences of re-isolated fungal isolates from the tested peppers were the same as the original isolate. To our knowledge, this is the first report of F. incarnatum (synonym of F. semitectum) causing fruit rot on chili pepper in China. F. incarnatum has been reported to cause root rot of greenhouse pepper in China (Li et al. 2018), fruit rot of bell pepper in Trinidad (Ramdial et al. 2016) and Pakistan (Tariq et al. 2018). Effective control strategies need to be developed to prevent the economic losses caused by the disease in chili pepper.
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http://dx.doi.org/10.1094/PDIS-09-19-1996-PDNDOI Listing
March 2021

Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy.

ACS Med Chem Lett 2021 Mar 2;12(3):494-501. Epub 2021 Mar 2.

Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543-4000, United States.

Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958151PMC
March 2021

The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges.

Biomed Pharmacother 2021 Jun 6;138:111450. Epub 2021 Mar 6.

Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang, China. Electronic address:

Lung cancer is one of the common malignant tumors that threaten human life with serious incidence and high mortality. According to the histopathological characteristics, lung cancer is mainly divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for about 80-85% of lung cancers. In fact, lung cancer metastasis is a major cause of treatment failure in clinical patients. The underlying reason is that the mechanisms of lung cancer metastasis are still not fully understood. The metastasis of lung cancer cells is controlled by many factors, including the interaction of various components in the lung cancer microenvironment, epithelial-mesenchymal transition (EMT) transformation, and metastasis of cancer cells through blood vessels and lymphatics. The molecular relationships are even more intricate. Further study on the mechanisms of lung cancer metastasis and in search of effective therapeutic targets can bring more reference directions for clinical drug research and development. This paper focuses on the factors affecting lung cancer metastasis and connects with related molecular mechanisms of the lung cancer metastasis and mechanisms of lung cancer to specific organs, which mainly reviews the latest research progress of NSCLC metastasis. Besides, in this paper, experimental models of lung cancer and metastasis, mechanisms in SCLC transfer and the challenges about clinical management of lung cancer are also discussed. The review is intended to provide reference value for the future research in this field and promising treatment clues for clinical patients.
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http://dx.doi.org/10.1016/j.biopha.2021.111450DOI Listing
June 2021

The role of gut microbiota in tumorigenesis and treatment.

Biomed Pharmacother 2021 Jun 2;138:111444. Epub 2021 Mar 2.

Department of Endocrinology, the First Affiliated Hospital of Huzhou University, Huzhou, China. Electronic address:

A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.
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http://dx.doi.org/10.1016/j.biopha.2021.111444DOI Listing
June 2021

The impact of autologous versus implant-based breast reconstruction on body mass index in breast cancer patients.

Breast J 2021 Mar 3. Epub 2021 Mar 3.

Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1111/tbj.14214DOI Listing
March 2021

How to overcome the side effects of tumor immunotherapy.

Biomed Pharmacother 2020 Oct 20;130:110639. Epub 2020 Aug 20.

Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, 524023, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, 524023, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang, 524023, China. Electronic address:

The incidence of cancer is increasing year by year. Cancer has become one of the health threats of modern people. Simply relying on the surgery, chemotherapy or radiotherapy, not only the survival rate is not high, but also the quality of life of patients is not much better. Fortunately, the emergence and rapid development of cancer immunotherapy have brought more and more exciting results. However, when scientists think it is possible to overcome cancer, they find that not all cancer patients can benefit from immunotherapy, that is to say, the overall efficiency of immunotherapy is not high. Drug resistance and side effects of immunotherapy cannot be ignored. In order to overcome these difficulties, scientists continue to improve the strategy of immunotherapy and find that combination therapy can effectively reduce the incidence of drug resistance. They also found that by reprogramming tumor blood vessels, activating ferroptosis, utilizing thioredoxin, FATP2 and other substances, the therapeutic effect can be improved and side effects can be alleviated. This article reviews the principles of immunotherapy, new strategies to overcome drug resistance of cancer immunotherapy, and how to improve the efficacy of immunotherapy and reduce side effects.
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http://dx.doi.org/10.1016/j.biopha.2020.110639DOI Listing
October 2020

Characteristic Evaluation and Process Simulation of CuFeO as Oxygen Carriers in Coal Chemical Looping Gasification.

ACS Omega 2021 Feb 8;6(7):4783-4792. Epub 2021 Feb 8.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing 210096, China.

Chemical looping gasification (CLG) has been described as an innovative and low-cost gasification technology to convert carbonaceous fuels into synthesis gases. Oxygen carrier (OC) is the key to resolve the contradiction between rapid carbon conversion and appropriate partial oxidation of coal. At present, the solid fuel conversion in the CLG process is limited by an iron-based OC, and a copper-based carrier has difficulty in maintaining the reduction atmosphere. Hence, CuFeO has been proposed as a high-performance OC because of its synergistic effect. The present study first conducted a characteristic evaluation on CuFeO, including the reducibility and oxygen release capacity. The results showed that the addition of copper made a great contribution to the reduction process, and the presence of ferrite better relieved the deep oxygen loss of CuFeO. The thermodynamic limitation and evolution behavior of CuFeO in the reduction process were discussed for the simulation. An Aspen model of the CLG process with coal as the fuel and CuFeO as the OC was then established and validated by the experimental data. By consideration of the high carbon conversion and high syngas productivity in the operation, an OC/fuel mass ratio of approximately 1.25-2.25 and a gasification temperature range of 800-900 °C were thought to be optimal in the coal CLG process.
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http://dx.doi.org/10.1021/acsomega.0c05691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905827PMC
February 2021

Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1.

ACS Med Chem Lett 2021 Feb 28;12(2):288-294. Epub 2021 Jan 28.

Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase enzyme implicated in cancer immune response. This account details the discovery of BMS-986242, a novel IDO1 inhibitor designed for the treatment of a variety of cancers including metastatic melanoma and renal cell carcinoma. Given the substantial interest around this target for cancer immunotherapy, we sought to identify a structurally differentiated clinical candidate that performs comparably to linrodostat (BMS-986205) in terms of both potency and pharmacodynamic effect in a mouse xenograft model. On the basis of its preclinical profile, BMS-986242 was selected as a candidate for clinical development.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883469PMC
February 2021

Biomimetic mineralized hybrid scaffolds with antimicrobial peptides.

Bioact Mater 2021 Aug 22;6(8):2250-2260. Epub 2021 Jan 22.

Minnesota Dental Research Center for Biomaterials and Biomechanics, Department of Restorative Sciences, School of Dentistry, University of Minnesota, MN, 55455, USA.

Infection in hard tissue regeneration is a clinically-relevant challenge. Development of scaffolds with dual function for promoting bone/dental tissue growth and preventing bacterial infections is a critical need in the field. Here we fabricated hybrid scaffolds by intrafibrillar-mineralization of collagen using a biomimetic process and subsequently coating the scaffold with an antimicrobial designer peptide with cationic and amphipathic properties. The highly hydrophilic mineralized collagen scaffolds provided an ideal substrate to form a dense and stable coating of the antimicrobial peptides. The amount of hydroxyapatite in the mineralized fibers modulated the rheological behavior of the scaffolds with no influence on the amount of recruited peptides and the resulting increase in hydrophobicity. The developed scaffolds were potent by contact killing of Gram-negative and Gram-positive as well as cytocompatible to human bone marrow-derived mesenchymal stromal cells. The process of scaffold fabrication is versatile and can be used to control mineral load and/or intrafibrillar-mineralized scaffolds made of other biopolymers.
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http://dx.doi.org/10.1016/j.bioactmat.2020.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829078PMC
August 2021

Prevalence of and risk factors associated with sleep disturbances among HPCD exposed to COVID-19 in China.

Sleep Med 2021 04 6;80:16-22. Epub 2021 Jan 6.

Transplantation Center, The Third Xiangya Hospital of Central South University, Changsha, China; The Nursing School of Central South University, Changsha, 410000, China. Electronic address:

Objective: To assess sleep disturbances and associated factors among front-line healthcare providers who have been called upon for, dispatched (HPCD) and exposed to COVID-19 in China.

Methods: This cross-sectional, survey-based, isolation area-stratified study collected demographic data, sleep status and emotional measurements from 1036 HPCD in nine medical institutions from March 5 to 9, 2020 in Wuhan, China, which was the epicenter of the epidemic. HPCD who worked in isolation areas with COVID-19 were eligible for inclusion. The severity of symptoms of sleep disorders, insomnia and emotional self-efficacy were assessed by the Chinese versions of the 10-item Self-rating sleeping situation scale, the seven-item Insomnia Severity Index and the 12-item Regulatory emotional self-efficacy questionnaire, respectively. Univariate analysis was performed to identify factors associated with sleep disturbances. A structural equation model (SEM) was constructed via AMOS to explore the relationship among the four components.

Results: A total of 1036 out of 1075 contacted individuals completed the survey, with a participation rate of 96.4%. A total of 925 (89.3%) were aged 20-39 years, and 755 (72.9%) were women. Among all participants, 874 (84.4%) were nurses, and 162 (15.6%) were physicians; 538 (51.9%) worked in intensive care isolation units; 843 (81.4%) worked in isolation areas for 4 h straight, and 395 (38.1%) perceived COVID-19 peer exposure. A considerable proportion of participants reported symptoms of sleep disorders (543, 52.4%). Exposure status and length of work were the main factors affecting sleep status, which had indirect effects on sleep status by mediating regulatory emotional self-efficacy.

Conclusions: In this survey of HPCD for patients with COVID-19 in China, participants reported experiencing sleep disturbance burdens, especially those having exposure experience and working long shifts. Regulatory emotional self-efficacy (RESE) is an important resource for alleviating sleep disturbances and improving sleep quality. These findings emphasize the importance of being prepared to support HPCD through psychological interventions.
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http://dx.doi.org/10.1016/j.sleep.2020.12.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834103PMC
April 2021

Polyphenols Weaken Pea Protein Gel by Formation of Large Aggregates with Diminished Noncovalent Interactions.

Biomacromolecules 2021 Feb 26;22(2):1001-1014. Epub 2021 Jan 26.

Department of Food Science and Technology, The Ohio State University, 2015 Fyffe Rd, Columbus, Ohio 43210, United States.

Polyphenols are well-known native cross-linkers and gel strengthening agents for many animal proteins. However, their role in modifying plant protein gels remains unclear. In this study, multiple techniques were applied to unravel the influence of green tea polyphenols (GTP) on pea protein gels and the underlying mechanisms. We found that the elasticity and viscosity of pea protein gels decreased with increased GTP. The protein backbone became less rigid when GTP was present based on shortened T in relaxation solid-state NMR measurements. Electron microscopy and small-angle X-ray scattering showed that gels weakened by GTP possessed disrupted networks with the presence of large protein aggregates. Solvent extraction and molecular dynamic simulation revealed a reduction in hydrophobic interactions and hydrogen bonds among proteins in gels containing GTP. The current findings may be applicable to other plant proteins for greater control of gel structures in the presence of polyphenols, expanding their utilization in food and biomedical applications.
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http://dx.doi.org/10.1021/acs.biomac.0c01753DOI Listing
February 2021

Population Pharmacokinetics of Levetiracetam: A Systematic Review.

Clin Pharmacokinet 2021 Mar 15;60(3):305-318. Epub 2021 Jan 15.

Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030, People's Republic of China.

Background: Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy.

Objective: The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates.

Methods: We systematically searched the PubMed and Embase databases from inception to 30 June 2020. The information on study designs, target population, model characteristics, and identified covariates was summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults.

Results: Fourteen studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved adults only. The median value of apparent clearance for children (0.074 L/h/kg [range 0.038-0.079]) was higher than that for adults (0.054 L/h/kg [range 0.039-0.061]). Body weight was found to significantly influence the apparent clearance and volume of distribution, whereas renal function influenced the clearance. Likewise, coadministration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9-22%, whereas coadministration with valproate acid decreased it by 18.8%.

Conclusion: Levetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.
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http://dx.doi.org/10.1007/s40262-020-00963-2DOI Listing
March 2021

Cardiovascular disease in patients with COVID-19: evidence from cardiovascular pathology to treatment.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(3):273-282

Guangxi Key Laboratory of Diabetic Systems Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin 541100, China.

The coronavirus disease-2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly developed into a global pneumonia pandemic. Cardiovascular disease is the major comorbidity of COVID-19 patients and is closely related to the severity of COVID-19. SARS-CoV-2 infection can directly or indirectly cause a series of cardiac complications, including acute myocardial injury and myocarditis, heart failure and cardiac arrest, arrhythmia, acute myocardial infarction, cardiogenic shock, Takotsubo cardiomyopathy, and coagulation abnormalities. Intensive research on the SARS-CoV-2-associated cardiovascular complications is urgently needed to elucidate its exact mechanism and to identify potential drug targets, which will help to formulate effective prevention and treatment strategies. Hence, this review will summarize recent progress regarding the effects of COVID-19 on the cardiovascular system and describe the underlying mechanism of cardiovascular injury caused by SARS-CoV-2.
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http://dx.doi.org/10.1093/abbs/gmaa176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929476PMC
March 2021

The epitranscriptome of long noncoding RNAs in metabolic diseases.

Clin Chim Acta 2021 Apr 7;515:80-89. Epub 2021 Jan 7.

The Second Affiliated Hospital of Guilin Medical University, Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin, Guangxi 541100, China. Electronic address:

Long noncoding RNAs (lncRNAs) have abundant content and extensive functions that regulate the expression of genes at multiple levels. Recently, transcriptome-wide analysis confirmed that RNA can undergo various chemical modifications in response to stimulation by the environment that further determine the action mechanisms of RNAs and expand the diversity of the transcriptome. Modifications that occur in lncRNAs can affect their expression and the regulation of downstream molecules by changing the secondary structure, splicing, degradation or molecular stability of lncRNAs. During the development of metabolic diseases, reversible RNA modifications show a complex transcriptional landscape. Although a wide quantity and variety of lncRNA modifications have been identified, the knowledge regarding their underlying actions in alcohol use disorders (AUDs), osteoporosis, obesity, and cardiovascular disease (CVD) is still in its infancy. Herein, we will focus on the epitranscriptomic modifications that occur on lncRNAs and the crosstalk between them that affect metabolic diseases.
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http://dx.doi.org/10.1016/j.cca.2021.01.001DOI Listing
April 2021

AtHAP5A regulates iron translocation in iron-deficient Arabidopsis thaliana.

J Integr Plant Biol 2020 Dec 20;62(12):1910-1925. Epub 2020 Jul 20.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China.

Iron (Fe) deficient plants employ multiple strategies to increase root uptake and root-to-shoot translocation of Fe. The identification of genes that are responsible for these processes, and a comprehensive understanding of the regulatory effects of transcriptional networks on their expression, including transcription factors (TFs), is underway in Arabidopsis thaliana. Here, we show that a Histone- or heme-associated proteins (HAP) transcription factor (TF), HAP5A, is necessary for the response to Fe deficiency in Arabidopsis. Its expression was induced under Fe deficiency, and the lack of HAP5A significantly decreased Fe translocation from the root to the shoot, resulting in substantial chlorosis of the newly expanded leaves, compared with the wild-type (WT, Col-0). Further analysis found that the expression of a gene encoding nicotianamine (NA) synthase (NAS1) was dramatically decreased in the hap5a mutant, regardless of the Fe status. Yeast-one-hybrid and ChIP analyses suggested that HAP5A directly binds to the promoter region of NAS1. Moreover, overexpression of NAS1 could rescue the chlorosis phenotype of hap5a in Fe deficient conditions. In summary, a novel pathway was elucidated, showing that NAS1-dependent translocation of Fe from the root to the shoot is controlled by HAP5A in Fe-deficient Arabidopsis thaliana.
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http://dx.doi.org/10.1111/jipb.12984DOI Listing
December 2020

Imaging genomics for accurate diagnosis and treatment of tumors: A cutting edge overview.

Biomed Pharmacother 2021 Mar 28;135:111173. Epub 2020 Dec 28.

Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, China. Electronic address:

Imaging genomics refers to the establishment of the connection between invasive gene expression features and non-invasive imaging features. Tumor imaging genomics can not only understand the macroscopic phenotype of tumor, but also can deeply analyze the cellular and molecular characteristics of tumor tissue. In recent years, tumor imaging genomics has been a key in the field of medicine. The incidence of cancer in China has increased significantly, which is the main reason of disease death of urban residents. With the rapid development of imaging medicine, depending on imaging genomics, many experts have made remarkable achievements in tumor screening and diagnosis, prognosis evaluation, new treatment targets and understanding of tumor biological mechanism. This review analyzes the relationship between tumor radiology and gene expression, which provides a favorable direction for clinical staging, prognosis evaluation and accurate treatment of tumors.
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http://dx.doi.org/10.1016/j.biopha.2020.111173DOI Listing
March 2021

Breakthrough in targeted therapy for non-small cell lung cancer.

Biomed Pharmacother 2021 Jan 4;133:111079. Epub 2020 Dec 4.

Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, China. Electronic address:

Non-small cell lung cancer (NSCLC) remains by far the single most common malignancy of lung cancer which causes more and more mortality in recent years. NSCLC accounts for more than 80 % of lung cancers, and the vast majority of patients were found to be in advanced inoperable stages. Chemotherapy used to be the main treatment for NSCLC, but due to its obvious side effects. Chemotherapy gradually withdrew from the stage of history. In recent years, cellular and molecular biotechnology has developed rapidly, and researchers have begun to target key genes and regulatory molecules for treatment. Targeted drugs have also emerged. The purpose of this review is to introduce important research achievements in recent years and the treatment progress of new drugs.
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http://dx.doi.org/10.1016/j.biopha.2020.111079DOI Listing
January 2021

How wide is the application of genetic big data in biomedicine.

Biomed Pharmacother 2021 Jan 9;133:111074. Epub 2020 Dec 9.

Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, China. Electronic address:

In the era of big data, massive genetic data, as a new industry, has quickly swept almost all industries, especially the pharmaceutical industry. As countries around the world start to build their own gene banks, scientists study the data to explore the origins and migration of humans. Moreover, big data encourage the development of cancer therapy and bring good news to cancer patients. Big datum has been involved in the study of many diseases, and it has been found that analyzing diseases at the gene level can lead to more beneficial treatment options than ordinary treatments. This review will introduce the development of extensive data in medical research from the perspective of big data and tumor, neurological and psychiatric diseases, cardiovascular diseases, other applications and the development direction of big data in medicine.
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http://dx.doi.org/10.1016/j.biopha.2020.111074DOI Listing
January 2021

A Hyperspectral Image Classification Approach Based on Feature Fusion and Multi-Layered Gradient Boosting Decision Trees.

Entropy (Basel) 2020 Dec 25;23(1). Epub 2020 Dec 25.

College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China.

At present, many Deep Neural Network (DNN) methods have been widely used for hyperspectral image classification. Promising classification results have been obtained by utilizing such models. However, due to the complexity and depth of the model, increasing the number of model parameters may lead to an overfitting of the model, especially when training data are insufficient. As the performance of the model mainly depends on sufficient data and a large network with reasonably optimized hyperparameters, using DNNs for classification requires better hardware conditions and sufficient training time. This paper proposes a feature fusion and multi-layered gradient boosting decision tree model (FF-DT) for hyperspectral image classification. First, we fuse extended morphology profiles (EMPs), linear multi-scale spatial characteristics, and nonlinear multi-scale spatial characteristics as final features to extract both special and spectral features. Furthermore, a multi-layered gradient boosting decision tree model is constructed for classification. We conduct experiments based on three datasets, which in this paper are referred to as the Pavia University, Indiana Pines, and Salinas datasets. It is shown that the proposed FF-DT achieves better performance in classification accuracy, training conditions, and time consumption than other current classical hyperspectral image classification methods.
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http://dx.doi.org/10.3390/e23010020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824154PMC
December 2020

Nanomedicines: Redefining traditional medicine.

Biomed Pharmacother 2021 Feb 15;134:111103. Epub 2020 Dec 15.

Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China. Electronic address:

Nanomedicines offer nanoscale drug delivery system. They offer ways of promising drug transportation, and address the issues of lack of targeting and permeability of traditional drugs. The physical and chemical properties in the domain of nanomedicine applications in vivo have not been sufficiently delivered. What's more, the metabolic of nanomedicines is not clear enough. Those factors which mentioned above determine that many nanomedicines have not yet realized clinical application due to their safety problems and in vivo efficacy. For example, they may cause immune response and cytotoxicity, as well as the ability to clear organs in vivo, the penetration ability of them and the lack of targeting ability may also cause poor efficacy of drugs in vivo. In this review, the new progresses of different kinds of nanomedicines (including gold nanoparticles, nanorobots, black phosphorus nanoparticles, brain diseases, gene editing and immunotherapy etc.) in anti-tumor, antibacterial, ocular diseases and arteriosclerosis in recent years were summarized. Their shortcomings were pointed out, and the new methods to improve the biosafety and efficacy were summarized.
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http://dx.doi.org/10.1016/j.biopha.2020.111103DOI Listing
February 2021

Modelling and Phenotypic Screening of NAP-6 and 10-Cl-BBQ, AhR Ligands Displaying Selective Breast Cancer Cytotoxicity in Vitro.

ChemMedChem 2020 Dec 9. Epub 2020 Dec 9.

Chemistry, School of Environmental & Life Sciences, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.

To exploit the interaction of the aryl hydrocarbon receptor (AhR) pathway in developing breast-cancer-specific cytotoxic compounds, we examined the breast cancer selectivity and the docking pose of the AhR ligands (Z)-2-(2-aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (NAP-6; 5) and 10-chloro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (10-Cl-BBQ; 6). While the breast cancer selectivity of 5 in vitro is known, we discuss the SAR around this lead and, by using phenotypic cell-line screening and the MTT assay, show for the first time that 6 also presents with breast cancer selectivity, notably in the triple-negative (TN) receptor breast cancer cell line MDA-MB-468, the ER+ breast cancer cell lines T47D, ZR-75-1 and the HER2+ breast cancer cell line SKBR3 (GI values of 0.098, 0.97, 0.13 and 0.21 μM, respectively). Indeed, 6 is 55 times more potent in MDA-MB-468 cells than normal MCF10A breast cells (GI of 0.098 vs 5.4 μM) and more than 130 times more potent than in cell lines derived from pancreas, brain and prostate (GI of 0.098 vs 10-13 μM). Molecular docking poses of 5 and 6 together with analogue synthesis and phenotypic screening show the importance of the naphthalene moiety, and an ortho-disposed substituent on the N-phenyl moiety for biological activity.
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http://dx.doi.org/10.1002/cmdc.202000721DOI Listing
December 2020

Automatic registration of a single SAR image and GIS building footprints in a large-scale urban area.

ISPRS J Photogramm Remote Sens 2020 Dec;170:1-14

Remote Sensing Technology Institute, German Aerospace Center (DLR), Münchener Straße 20, 82234 Weßling, Germany.

Existing techniques of 3-D reconstruction of buildings from SAR images are mostly based on multibaseline SAR interferometry, such as PSI and SAR tomography (TomoSAR). However, these techniques require tens of images for a reliable reconstruction, which limits the application in various scenarios, such as emergency response. Therefore, alternatives that use a single SAR image and the building footprints from GIS data show their great potential in 3-D reconstruction. The combination of GIS data and SAR images requires a precise registration, which is challenging due to the unknown terrain height, and the difficulty in finding and extracting the correspondence. In this paper, we propose a framework to automatically register GIS building footprints to a SAR image by exploiting the features representing the intersection of ground and visible building facades, specifically the near-range boundaries in the building polygons, and the double bounce lines in the SAR image. Based on those features, the two data sets are registered progressively in multiple resolutions, allowing the algorithm to cope with variations in the local terrain. The proposed framework was tested in Berlin using one TerraSAR-X High Resolution SpotLight image and GIS building footprints of the area. Comparing to the ground truth, the proposed algorithm reduced the average distance error from 5.91 m before the registration to -0.08 m, and the standard deviation from 2.77 m to 1.12 m. Such accuracy, better than half of the typical urban floor height (3 m), is significant for precise building height reconstruction on a large scale. The proposed registration framework has great potential in assisting SAR image interpretation in typical urban areas and building model reconstruction from SAR images.
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http://dx.doi.org/10.1016/j.isprsjprs.2020.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694880PMC
December 2020

Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children.

PLoS Negl Trop Dis 2020 12 7;14(12):e0008886. Epub 2020 Dec 7.

Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.

Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10-15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy.
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http://dx.doi.org/10.1371/journal.pntd.0008886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746298PMC
December 2020

Adjustable and stable beam profile generation in a Yb:YAG thin-disk laser.

Opt Lett 2020 Dec;45(23):6550-6553

We present a Yb:YAG thin-disk laser with an adjustable and stable beam profile. A double-cavity geometry with an acousto-optic modulator (AOM) makes the spatial separation of the gain area, in which the central and external parts are used for and mode generation, respectively. By changing the loss of the AOM, the beam profile of the primary cavity is adjustable from annularity to flat-top continuously. At input pump power of 44 W, 8.5 W annular, 11.1 W shallow crater-shaped, and 12.1 W flat-topped modes were obtained. Moreover, the thin-disk laser with a multi-pass pumping scheme not only improves thermal management, but also minimizes depolarization loss, allowing the optimization of mode stability and laser performances. This Letter implies that a high-power laser with an adjustable and stable beam profile can be implemented via this scheme.
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http://dx.doi.org/10.1364/OL.412599DOI Listing
December 2020

Meltblown fabric nanofiber membrane, which is better for fabricating personal protective equipments.

Chin J Chem Eng 2020 Nov 23. Epub 2020 Nov 23.

State Key Laboratory of Materials-Oriented Chemical Engineering, National Engineering Research Center for Special Separation Membrane, Nanjing Tech University, Nanjing 210009, China.

The coronavirus disease 2019 (COVID-19) pandemic has led to a great demand on the personal protection products such as reusable masks. As a key raw material for masks, meltblown fabrics play an important role in rejection of aerosols. However, the electrostatic dominated aerosol rejection mechanism of meltblown fabrics prevents the mask from maintaining the desired protective effect after the static charge degradation. Herein, novel reusable masks with high aerosols rejection efficiency were fabricated by the introduction of spider-web bionic nanofiber membrane (nano cobweb-biomimetic membrane). The reuse stability of meltblown and nanofiber membrane mask was separately evaluated by infiltrating water, 75% alcohol solution, and exposing under ultraviolet (UV) light. After the water immersion test, the filtration efficiency of meltblown mask was decreased to about 79%, while the nanofiber membrane was maintained at 99%. The same phenomenon could be observed after the 75% alcohol treatment, a high filtration efficiency of 99% was maintained in nanofiber membrane, but obvious negative effect was observed in meltblown mask, which decreased to about 50%. In addition, after long-term expose under UV light, no filtration efficiency decrease was observed in nanofiber membrane, which provide a suitable way to disinfect the potential carried virus. This work successfully achieved the daily disinfection and reuse of masks, which effectively alleviate the shortage of masks during this special period.
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http://dx.doi.org/10.1016/j.cjche.2020.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682934PMC
November 2020