Publications by authors named "Rong Wang"

2,136 Publications

  • Page 1 of 1

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omics.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

BGI-Shenzhen, Shenzhen 518083, China.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, and cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancy, delivery histories, cesarean section, and breast-feeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breast-feeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiome, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
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http://dx.doi.org/10.1016/j.gpb.2021.01.005DOI Listing
June 2021

Enhanced isomerization of rare sugars by ribose-5-phosphate isomerase A from Ochrobactrum sp. CSL1.

Enzyme Microb Technol 2021 Aug 26;148:109789. Epub 2021 Mar 26.

School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou, 215009, PR China. Electronic address:

Ribose-5-phosphate isomerase A (RpiA) is of great importance in biochemistry research, however its application in biotechnology has not been fully explored. In this study the activity of RpiA from Ochrobactrum sp. CSL1 (OsRpiA) towards D-allose was engineered based on sequential and structural analyses. Strategies of alanine scanning, rational design and saturated mutagenesis were employed to create three mutant libraries. A single mutant of K124A showed a 45 % activity improvement towards D-allose. The reaction properties of the mutant were analyzed, and a shift of optimal pH and higher thermal stability at low reaction temperatures were identified. The conversion of D-allose was also improved by 40 % using K124A, and higher activities on major substrates were found in the mutant's substrate scope, implying its application potential in rare sugar preparation. Kinetics analysis revealed that K of K124A mutant decreased by 12 % and the catalytic efficiency increased by 65 % towards D-allose. Moreover, molecular dynamics simulation illustrated the binding of substrate and K124A was more stable than that of the wild-type. The shorter distance and more relax bond angle between the catalytic residue of K124A and D-allose explained the activity improvement in detail. This study highlights the potential of OsRpiA as a biocatalyst for rare sugar preparation, and provides distinct evidences for its catalytic mechanism.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109789DOI Listing
August 2021

Serum TBA and GCA Levels Across Pregnancy and the Gestational Age-Specific Reference Intervals for Pregnant Chinese.

Clin Lab 2021 Jun;67(6)

Background: Reference intervals of clinical laboratory indexes are the basis of interpretation of test results. While intrahepatic cholestasis of pregnancy (ICP) could severely threaten maternal and fetal health, reference intervals of the biomarkers serum total bile acids (TBA) and glycocholic acid (GCA) are unsatisfactory. The purpose of this study was to derive gestational age-specific reference intervals for serum TBA and GCA in a Chinese population to promote early diagnosis of ICP.

Methods: A total of 416 healthy pregnant Chinese were recruited and divided into three groups by gestational age: 140 in the first trimester (1 - 13 weeks) group, 136 in the second trimester (14 - 27 weeks) group, and 140 in the third trimester (≥ 28 weeks) group. Serum TBA and GCA levels were measured respectively by cyclic enzymatic method and latex enhanced immune turbidimetry. Reference intervals were calculated with non-parametric method.

Results: The reference intervals of serum TBA are 0.90 - 6.60 μmol/L, 1.20 - 9.10 μmol/L, and 1.50 - 8.90 μmol/L respectively in the first, second, and third trimester. The reference intervals of serum GCA are 0.24 - 1.14 μg/mL in the first and second trimesters (combined) and 0.00 - 2.04 μg/mL in the third trimester.

Conclusions: Gestational age-specific reference intervals of serum TBA and GCA for pregnant Chinese were derived in strict accordance with CLSI C28-A3 guidelines, which will be valuable for early diagnosis of ICP.
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http://dx.doi.org/10.7754/Clin.Lab.2020.201043DOI Listing
June 2021

Progress of photothermal membrane distillation for decentralized desalination: A review.

Water Res 2021 May 27;201:117299. Epub 2021 May 27.

Singapore Membrane Technology Centre, Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, Singapore 637141, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.

The conventional membrane distillation (MD) process is accompanied by large energy consumption, low thermal efficiency and inevitable requirements of centralized infrastructures, which impede its practical applications, especially in the offshore and remote off-grid areas. Thanks to the rapid development of efficient photothermal materials over the last decade, a new photothermal membrane distillation (PMD) process has emerged to harness abundant solar energy and localize heating on the membrane-feed water interface via photothermal effects. Driven by the temperature difference across the PMD membrane, water vapor can be generated on the membrane-feed surface, transported through membrane pores and condensed at permeate side to obtain freshwater, thus tackling the challenge of obtaining clean water using green energy. The PMD process avoids heating the entire bulk feed water and feed transportation from heat units to membrane modules, which save substantial amounts of energy. The interfacial localized heating intrinsically mitigates the temperature polarization across the membrane. The latent heat from vapor condensation can be effectively recovered via multi-level PMD configurations. As great efforts have been made to exploit PMD process, it is imperative to review the state-of-the-art progress of PMD and shed light on its future trend. Here, we briefly illustrate PMD mechanisms and membrane requirements, photothermal materials feasible for developing PMD membranes along with their light-to-heat mechanisms. This is followed by reviewing diverse approaches to prepare PMD membranes, which are classified into one-step fabrication and multi-step modification methods. Comprehensive discussion about PMD membrane performance in different configurations and their small pilot-scaled applications are provided. The effects of operational parameters and module designs are discussed in Section 6. Finally, the current challenges and future perspectives of PMD process are emphasized with the aim of providing guidance for future works.
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http://dx.doi.org/10.1016/j.watres.2021.117299DOI Listing
May 2021

SOX14 hypermethylation as a tumour biomarker in cervical cancer.

BMC Cancer 2021 Jun 7;21(1):675. Epub 2021 Jun 7.

Department of Laboratory Medicine, Tianjin Medical University, Tianjin, China.

Background: The association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer.

Methods: First, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROC.

Results: Pooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37.

Conclusion: SOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer.
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http://dx.doi.org/10.1186/s12885-021-08406-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185922PMC
June 2021

Targeted DNA profiling and the prevalence of NTRK aberrations in Chinese patients with head and neck cancer.

Oral Oncol 2021 Jun 4;119:105369. Epub 2021 Jun 4.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Objectives: Head and neck cancers are aggressive epithelial tumours that are recognised as being particularly challenging to treat. Here, we report the targeted DNA profiling and the prevalence of neurotrophic-tropomyosin receptor tyrosine kinase gene (NTRK) aberrations in Chinese patients with head and neck cancers.

Methods: Samples of 127 patients with head and neck cancer were retrospectively analysed. Profiling was performed by next-generation sequencing of the 1021-gene panel with tumour tissue and matched peripheral blood control samples.

Results: This study was inspired by the outcome benefit of a parotid cancer patient harbouring ETV6-NTRK3 fusion, who received crizotinib treatment and achieved a 2-year progression-free survival. Genomic profiling of 127 patients with head and neck cancers indicated that TP53 is the most frequently mutated gene both in our cohort and in The Cancer Genome Atlas (TCGA) database. A higher prevalence of NTRK genetic aberrations (7.9%, 10/127), including NTRK fusion (3.1%) and mutation, was observed in our population than in TCGA. The most common fusion was the ETV6-NTRK3. Compared to the NTRK-wt group, the NTRK aberration group had more APC and PTPRD aberrations (p < 0.05). NTRK fusion was also associated with lower tumour mutation burden (TMB) (p < 0.05). TP53 and LRP1B mutations were significantly associated with higher TMB (both p < 0.01), which may be potential markers of immunotherapy.

Conclusions: This is the first study to report targeted DNA profiling of Chinese patients with head and neck cancers. As NTRK genetic aberrations are more common in this Chinese population, the efficacy of NTRK inhibitors should be studied further.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105369DOI Listing
June 2021

LncRNA PVT1 accelerates LPS-induced septic acute kidney injury through targeting miR-17-5p and regulating NF-κB pathway.

Int Urol Nephrol 2021 Jun 5. Epub 2021 Jun 5.

ICU Department, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei, China.

Background: Long noncoding RNA PVT1 is associated with diverse human diseases, including acute kidney injury (AKI). However, our understandings of PVT1 on septic AKI are limited.

Methods: The septic AKI model was constructed through lipopolysaccharide (LPS) treatment. PVT1 and miR-17-5p levels were measured using qRT-PCR analysis. The concentrations of inflammatory cytokines were determined with ELISA kits. Cell viability and apoptosis were assessed using CCK-8 assay and flow-cytometric analysis, respectively. Protein levels were examined using western blot assay. The targeting association between miR-17-5p and PVT1 was verified by dual-luciferase reporter, RIP and RNA pull-down assays.

Results: PVT1 level was elevated and miR-17-5p level was declined in septic AKI patients' serum and LPS-stimulated HK-2 cells. Cell viability was suppressed and cell apoptosis and inflammation were promoted after LPS treatment. PVT1 knockdown or miR-17-5p elevation restored LPS-mediated HK-2 cell injury. MiR-17-5p was sponged by PVT1, and its inhibition weakened the impact of PVT1 deficiency on LPS-mediated injury of HK-2 cells. In addition, PVT1 knockdown inactivated NF-κB pathway mediated by LPS treatment, but miR-17-5p inhibition further reversed this effect.

Conclusion: PVT1 knockdown promoted cell viability, suppressed inflammatory response and apoptosis by regulating miR-17-5p expression and NF-κB pathway in LPS-stimulated HK-2 cells.
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http://dx.doi.org/10.1007/s11255-021-02905-8DOI Listing
June 2021

Multiple endocrine neoplasia 2A with RET mutation p.Cys611Tyr: A case report.

Medicine (Baltimore) 2021 Jun;100(22):e26230

Department of Endocrinology and Metabolism, Longgang District People's Hospital of Shenzhen, The Third Affiliated Hospital (Provisional) of The Chinese University of Hong Kong, Longgang central city, Shenzhen, Guangdong, P.R. China.

Rationale: Multiple endocrine neoplasia 2A (MEN2A) is a rare autosomal-dominant genetic syndrome, frequently misdiagnosed or neglected clinically, resulting in delayed therapy to patients.

Patient Concerns: A 47-year-old Chinese male patient underwent laparoscopic right adrenal tumorectomy, and postoperative pathology confirmed the tumor as pheochromocytoma (PHEO). He was readmitted to the department of endocrinology and metabolism due to constant increase in carcinoembryonic antigen (CEA) at 5 months after the operation.

Diagnosis: The patient was confirmed with medullary thyroid carcinoma (MTC), multiple neck lymph node metastasis, and pituitary microadenoma. The p.Cys611Tyr (c.1832G>A, C611Y) mutation was detected. Therefore, he was diagnosed with MEN2A.

Interventions: He underwent total thyroidectomy. The gene-sequencing analysis of his family was conducted, and the C611Y mutation was detected in his daughter.

Outcomes: The level of carcinoembryonic antigen decreased significantly after thyroidectomy in this patient. Long-term follow-up management was conducted. Elevated serum calcitonin and bilateral thyroid nodules were found in his 13-year-old daughter. Thus, MEN2A was highly suspected and she was suggested to undergo total thyroidectomy.

Conclusion: Patients with MEN2A should be screened regularly and managed by a multidisciplinary team.
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http://dx.doi.org/10.1097/MD.0000000000026230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183697PMC
June 2021

Injectable Cryogels Associate with Adipose-Derived Stem Cells for Cardiac Healing After Acute Myocardial Infarctions.

J Biomed Nanotechnol 2021 May;17(5):981-988

Department of Cardiovascular Surgery, People's Liberation Army General Hospital, Beijing 100853, China.

Treatment of adipose-derived stem cells (ADSCs) provides support for novel methods of conveying baseline cell protein endothelial cells to promote acute myocardial infarction in gelatin sericin (GS) lamin-coated antioxidant systems ([email protected]). The ratio of fixity modules, pores, absorption, and inflammation in the range of ka (65 ka), 149 ±39.8 μm, 92.2%, 42 ± 1.38, and 29 ± 1.9 were observed in the synthesized frames for GS. Herein, [email protected] was prepared, and the relevant substance for the development of cardiac regenerative applications was stable and physically chemical. assessments of [email protected] injectable cryogels established the enhanced survival rates of the cell and improved pro- angiogenic factors as well as pro-inflammatory expression, confirming the favorable outcomes of fractional ejections, fibro-areas, and vessel densities with reduced infraction dimensions. The novel ADSC-injecting cryogel method could be useful for successful heart injury therapies during acute myocardial infarction. Additionally, the method could be useful for successful heart injury therapies during coronary heart disease.
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http://dx.doi.org/10.1166/jbn.2021.3082DOI Listing
May 2021

Cytokine levels at birth in children who developed acute lymphoblastic leukemia.

Cancer Epidemiol Biomarkers Prev 2021 Jun 2. Epub 2021 Jun 2.

Epidemiology, University of California, Berkeley, School of Public Health.

Background: Prenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL).

Methods: Seven cytokines - interleukin 1β (IL1β), IL4, IL6, IL8, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα), and vascular endothelial growth factor (VEGF) - were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. Odds ratios (ORs) and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression adjusting for sociodemographic and birth characteristics.

Results: We found that ALL patients were born with higher levels of a group of correlated cytokines than controls [IL1β: OR of 1.18 (95% CI: 1.03, 1.35); IL8: 1.19 (1.03, 1.38); TNFα: 1.15 (1.01, 1.30); VEGF: 1.16 (1.01, 1.33)], especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk.

Conclusions: We posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL.

Impact: This is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1704DOI Listing
June 2021

The predictive value of soluble osteoclast-associated receptor for the prognosis of acute coronary syndrome.

Sci Rep 2021 Jun 1;11(1):11412. Epub 2021 Jun 1.

The Department of General Practice, Affiliated Hospital 2 of Nantong University, No. 6, Hai'er Xiang North Road, Chongchuan District, Nantong, 226001, China.

At present, prognostic biomarkers of acute coronary syndrome (ACS) are fewer. The aim of this study was to explore the predictive value of soluble osteoclast-associated receptor (sOSCAR) level for the major adverse cardiovascular events (MACE) occurring within 30 days after ACS. From January to August 2020, a total of 108 patients with ACS who were admitted to our hospital, were enrolled in this study. Of the 108 patients, 79 were men and 29 women. Patient-related data, including age, sex, body mass index, history of type 2 diabetes, history of hyperlipidemia and serum sOSCAR level, were collected. All patients were followed up for 30 days. Based on MACE occurrence, the 108 patients were divided into MACE group (n = 17) and non-MACE group (n = 91). The baseline data were compared between the two groups, MACE-independent risk factors were identified by multivariate regression analysis, and the predictive value of sOSCAR for MACE occurring within 30 days after CAS was analyzed using receiver operating characteristic (ROC) curve. At the same time, according to the type of ACS, the 108 patients with ACS were divided into unstable angina (UA) group (n = 29), non ST-segment elevation myocardial infarction (USTEMI) group (n = 45) and ST-segment elevation myocardial infarction (STEMI) group (n = 34), and then the sOSCAR level and MACE incidence were observed in each group. The serum sOSCAR level was significantly lower in the MACE group [130(100,183)] than in the non-MACE group [301(220,370)] (P = 0.000). The area under ROC curve of sOSCAR level for MACE occurring within 30 days after CAS was 0.860 with 95%CI 0.782-0.919, P < 0.001. Multivariate regression analysis indicated that the sOSCAR level was an independent risk factor for the MACE occurring within 30 days after CAS (OR 0.26, 95%CI 0.087-0.777, P = 0.04). The MACE incidence (0%) was the lowest but the sOSCAR level was the highest in the UA group, while in the STEMI group, the MACE incidence (23.53%) was the higest but the sOSCAR level was the lowest among the UA, STEMI and NSTEMI groups. Serum sOSCAR level may be used as a predictor of MACE occurring within the short-term after ACS. The higher the sOSCAR level, the lower the MACE incidence.
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http://dx.doi.org/10.1038/s41598-021-91054-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169834PMC
June 2021

Segregation, integration, and balance of large-scale resting brain networks configure different cognitive abilities.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Department of Physics, Centre for Nonlinear Studies, Beijing-Hong Kong-Singapore Joint Centre for Nonlinear and Complex Systems (Hong Kong), Institute of Computational and Theoretical Studies, Hong Kong Baptist University, Hong Kong;

Diverse cognitive processes set different demands on locally segregated and globally integrated brain activity. However, it remains an open question how resting brains configure their functional organization to balance the demands on network segregation and integration to best serve cognition. Here we use an eigenmode-based approach to identify hierarchical modules in functional brain networks and quantify the functional balance between network segregation and integration. In a large sample of healthy young adults (n = 991), we combine the whole-brain resting state functional magnetic resonance imaging (fMRI) data with a mean-filed model on the structural network derived from diffusion tensor imaging and demonstrate that resting brain networks are on average close to a balanced state. This state allows for a balanced time dwelling at segregated and integrated configurations and highly flexible switching between them. Furthermore, we employ structural equation modeling to estimate general and domain-specific cognitive phenotypes from nine tasks and demonstrate that network segregation, integration, and their balance in resting brains predict individual differences in diverse cognitive phenotypes. More specifically, stronger integration is associated with better general cognitive ability, stronger segregation fosters crystallized intelligence and processing speed, and an individual's tendency toward balance supports better memory. Our findings provide a comprehensive and deep understanding of the brain's functioning principles in supporting diverse functional demands and cognitive abilities and advance modern network neuroscience theories of human cognition.
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http://dx.doi.org/10.1073/pnas.2022288118DOI Listing
June 2021

Two Different Inoculation Methods Unveiled the Relative Independence of DON Accumulation in Wheat Kernels from Disease Severity on Spike after Infection by Fusarium Head Blight.

Toxins (Basel) 2021 May 14;13(5). Epub 2021 May 14.

Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Key Laboratory of Plant Functional Genomics of the Ministry of Education/Collaborative-Innovation of Modern Crops and Food Crops in Jiangsu/Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China.

Fusarium head blight (FHB) causes wheat yield loss and mycotoxin (deoxynivalenol, DON) accumulation in wheat kernel. Developing wheat cultivars with overall resistance to both FHB spread within a spike and DON accumulation in kernels is crucial for ensuring food security and food safety. Here, two relatively novel inoculation methods, bilateral floret inoculation (BFI) and basal rachis internode injection (BRII), were simultaneously employed to evaluate disease severity and DON content in kernels in a segregating population of recombinant inbred lines (RILs) developed from Ning 7840 (carrying ) and Clark (without ). Under both inoculation methods, four contrasting combinations of disease severity and DON content were identified: high severity/high DON (HSHD), high severity/low DON (HSLD), low severity/high DON (LSHD) and low severity/low DON (LSLD). Unexpectedly, the BRII method clearly indicated that disease severity was not necessarily relevant to DON concentration. The effects of on disease severity, and on DON concentrations, agreed very well across the two methods. Several lines carrying showed extremely higher severity and (or) DON content under both inoculation methods. The "Mahalanobis distance" (MD) method was used to rate overall resistance of a line by inclusion of both disease severity and DON content over both methods to select LSLD lines.
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http://dx.doi.org/10.3390/toxins13050353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156083PMC
May 2021

Coordinate Descent Method for k-means.

IEEE Trans Pattern Anal Mach Intell 2021 Jun 1;PP. Epub 2021 Jun 1.

Original k-means method using Lloyd algorithm partitions a data set by minimizing a sum of squares cost function to find local minima, which can be used for data analysis and machine learning that shows promising performance. However, Lloyd algorithm suffers from finding bad local minima. In this paper, we use coordinate descent (CD) method to solve the problem. First, we show that the k-means minimization problem can be reformulated as a trace maximization problem, a simple and very efficient coordinate descent scheme is proposed to solve this problem later. The effectiveness of our method is illustrated on several real-world data sets with varing number of clusters, varing number of samples and varing number of dimensionalty. Extensive experiments conducted show that CD performs better compared to Lloyd, i.e., lower objective value and better local minima. What's more, the results show that CD is more robust to initialization than Lloyd method whether the initialization strategy is random or k-means++. In addition, according to the computational complexity analysis, it is verified CD has the same time complexity with original k-means method.
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http://dx.doi.org/10.1109/TPAMI.2021.3085739DOI Listing
June 2021

Spatially explicit analysis identifies significant potential for bioenergy with carbon capture and storage in China.

Nat Commun 2021 05 26;12(1):3159. Epub 2021 May 26.

Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science and Engineering, Fudan University, Shanghai, China.

As China ramped-up coal power capacities rapidly while CO emissions need to decline, these capacities would turn into stranded assets. To deal with this risk, a promising option is to retrofit these capacities to co-fire with biomass and eventually upgrade to CCS operation (BECCS), but the feasibility is debated with respect to negative impacts on broader sustainability issues. Here we present a data-rich spatially explicit approach to estimate the marginal cost curve for decarbonizing the power sector in China with BECCS. We identify a potential of 222 GW of power capacities in 2836 counties generated by co-firing 0.9 Gt of biomass from the same county, with half being agricultural residues. Our spatially explicit method helps to reduce uncertainty in the economic costs and emissions of BECCS, identify the best opportunities for bioenergy and show the limitations by logistical challenges to achieve carbon neutrality in the power sector with large-scale BECCS in China.
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http://dx.doi.org/10.1038/s41467-021-23282-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154910PMC
May 2021

Effects and safety of aspirin use in patients after cerebrovascular bypass procedures.

Stroke Vasc Neurol 2021 May 26. Epub 2021 May 26.

Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Object: Superficial temporal artery to middle cerebral artery (STA-MCA) bypass is the most effective treatment for Moyamoya disease (MMD). In this study, we aimed to assess whether aspirin improves STA-MCA bypass patency and is safe in patients with MMD.

Methods: We performed a retrospective medical record review of patients with ischaemic-onset MMD who had undergone STA-MCA bypass at two hospitals between January 2011 and August 2018, to clarify the effects and safety of aspirin following STA-MCA bypass. The neurological status at the last follow-up (FU) was compared between patients with FU bypass patency and occlusion.Among 217 identified patients (238 hemispheres), the mean age was 41.4±10.2 years, and 51.8% were male; the indications for STA-MCA bypass were stroke (48.2%), followed by a transient ischaemic attack (44.0%). Immediate bypass patency was confirmed in all cases. During the FU period (1.5±1.5 y), 15 cases were occluded at FU imaging, resulting in an overall cumulative patency rate of 94%. The patency rates were 93% and 94% in the short-term FU group (n=131, mean FU time 0.5±0.2 years) and long-term FU group (n=107, mean FU time 4.1±3.5 years), respectively. The STA-MCA bypass patency rate in the aspirin group was higher than that in the non-aspirin group (98.7% vs 89.7%; HR 1.57; 95% CI 1.106 to 2.235; p=0.012). No significant difference in the FU haemorrhagic events was observed between the aspirin and non-aspirin groups.

Conclusions: Among adult patients with ischaemic-onset MMD undergoing STA-MCA bypass procedures, aspirin might increase the bypass patency rate, without increasing the bleeding risk. FU bypass patency may be associated with a better outcome. Additional studies, especially carefully designed prospective studies, are needed to address the role of aspirin after bypass procedures.
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http://dx.doi.org/10.1136/svn-2020-000770DOI Listing
May 2021

Co-occurrence of and mutations defines an adverse prognostic core-binding factor acute myeloid leukemia.

Leuk Lymphoma 2021 May 24:1-10. Epub 2021 May 24.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was mutation (30.6%), followed by (24.2%) and (14.5%) mutations, which was associated with a higher number of bone marrow blasts ( = .049) and older age ( = .027). The survival analysis showed mutation adversely affected the overall survival (OS) ( = .046). mutation was associated with inferior OS ( = .016) and RFS ( = .039). Eight patients carried co-mutations of and and had worse OS ( = .012) and RFS ( = .034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of and were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML.
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http://dx.doi.org/10.1080/10428194.2021.1919660DOI Listing
May 2021

Optimization of -Phenylpropenoyl-l-amino Acids as Potent and Selective Inducible Nitric Oxide Synthase Inhibitors for Parkinson's Disease.

J Med Chem 2021 06 21;64(11):7760-7777. Epub 2021 May 21.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.

-Phenylpropenoyl-l-amino acids (NPAs) are inducible nitric oxide synthase (iNOS) inhibitors possessing preventive effects for Parkinson's disease (PD). Here, structural modifications for improving the iNOS inhibitory activity and blood-brain barrier (BBB) permeability of NPAs were conducted, leading to 20 optimized NPA derivatives (). Compound , with the most potent activity (IC = 74 nM), high BBB permeability ( = 19.1 × 10 cm/s), and high selectivity over other NOS isoforms, was selected as the lead compound. Further studies demonstrated that directly binds to iNOS. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced acute PD model, the oral administration of (1 and 2 mg/kg) exerted preventive effects by alleviating the loss of dopaminergic (DAergic) neurons. Notably, in the MPTP-/probenecid-induced chronic PD model, the same dose of also displayed a therapeutic effect by repairing the damaged DAergic neurons. Finally, good pharmacokinetic properties and low toxicity made a promising candidate for the treatment of PD.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00578DOI Listing
June 2021

The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions.

Sci Rep 2021 May 18;11(1):10548. Epub 2021 May 18.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.

MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.
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http://dx.doi.org/10.1038/s41598-021-89981-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131603PMC
May 2021

Molecular mechanisms of mutualistic and antagonistic interactions in a plant-pollinator association.

Nat Ecol Evol 2021 May 17. Epub 2021 May 17.

Center for Genomics and Biotechnology, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Key Laboratory of Genetics, Breeding and Multiple Utilization of Corps, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou, China.

Many insects metamorphose from antagonistic larvae into mutualistic adult pollinators, with reciprocal adaptation leading to specialized insect-plant associations. It remains unknown how such interactions are established at molecular level. Here we assemble high-quality genomes of a fig species, Ficus pumila var. pumila, and its specific pollinating wasp, Wiebesia pumilae. We combine multi-omics with validation experiments to reveal molecular mechanisms underlying this specialized interaction. In the plant, we identify the specific compound attracting pollinators and validate the function of several key genes regulating its biosynthesis. In the pollinator, we find a highly reduced number of odorant-binding protein genes and an odorant-binding protein mainly binding the attractant. During antagonistic interaction, we find similar chemical profiles and turnovers throughout the development of galled ovules and seeds, and a significant contraction of detoxification-related gene families in the pollinator. Our study identifies some key genes bridging coevolved mutualists, establishing expectations for more diffuse insect-pollinator systems.
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http://dx.doi.org/10.1038/s41559-021-01469-1DOI Listing
May 2021

Nomogram model to predict pneumothorax after computed tomography-guided coaxial core needle lung biopsy.

Eur J Radiol 2021 Jul 2;140:109749. Epub 2021 May 2.

Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, China. Electronic address:

Purpose: To develop a predictive model to determine risk factors of pneumothorax in patients undergoing the computed tomography (CT)-guided coaxial core needle lung biopsy (CCNB).

Methods: A total of 489 patients who underwent CCNBs with an 18-gauge coaxial core needle were retrospectively included. Patient characteristics, primary pulmonary disease, target lesion image characteristics and biopsy-related variables were evaluated as potential risk factors of pneumothorax which was determined on the chest X-ray and CT scans. Univariate and multivariate logistic regressions were used to identify the independent risk factors of pneumothorax and establish the predictive model, which was presented in the form of a nomogram. The discrimination and calibration of the model were evaluated as well.

Results: The incidence of pneumothorax was 32.91 % and 31.42 % in the development and validation groups, respectively. Age, emphysema, pleural thickening, lesion location, lobulation sign, and size grade were identified independent risk factors of pneumothorax at the multivariate logistic regression model. The forming model produced an area under the curve of 0.718 (95 % CI = 0.660-0.776) and 0.722 (95 % CI = 0.638-0.805) in development and validation group, respectively. The calibration curve showed good agreement between predicted and actual probability.

Conclusions: The predictive model for pneumothorax after CCNBs had good discrimination and calibration, which could help in clinical practice.
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http://dx.doi.org/10.1016/j.ejrad.2021.109749DOI Listing
July 2021

Mechanically Robust and UV-Curable Shape-Memory Polymers for Digital Light Processing Based 4D Printing.

Adv Mater 2021 May 17:e2101298. Epub 2021 May 17.

Shenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.

4D printing is an emerging fabrication technology that enables 3D printed structures to change configuration over "time" in response to an environmental stimulus. Compared with other soft active materials used for 4D printing, shape-memory polymers (SMPs) have higher stiffness, and are compatible with various 3D printing technologies. Among them, ultraviolet (UV)-curable SMPs are compatible with Digital Light Processing (DLP)-based 3D printing to fabricate SMP-based structures with complex geometry and high-resolution. However, UV-curable SMPs have limitations in terms of mechanical performance, which significantly constrains their application ranges. Here, a mechanically robust and UV-curable SMP system is reported, which is highly deformable, fatigue resistant, and compatible with DLP-based 3D printing, to fabricate high-resolution (up to 2 µm), highly complex 3D structures that exhibit large shape change (up to 1240%) upon heating. More importantly, the developed SMP system exhibits excellent fatigue resistance and can be repeatedly loaded more than 10 000 times. The development of the mechanically robust and UV-curable SMPs significantly improves the mechanical performance of the SMP-based 4D printing structures, which allows them to be applied to engineering applications such as aerospace, smart furniture, and soft robots.
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http://dx.doi.org/10.1002/adma.202101298DOI Listing
May 2021

Methacrylate-functionalized proanthocyanidins as novel polymerizable collagen cross-linkers - Part 1: Efficacy in dentin collagen bio-stabilization and cross-linking.

Dent Mater 2021 May 13. Epub 2021 May 13.

School of Dentistry, University of Missouri - Kansas City, Kansas City, MO, 64108, USA. Electronic address:

Objective: The aim of the study was to investigate the effects of methacrylate-functionalized proanthocyanidins (MAPAs) on dentin collagen's bio-stabilization against enzymatic degradation and crosslinking capability.

Methods: Three MAPAs were synthesized via varying methacrylate (MA) to proanthocyanidins (PA) feeding ratios of 1:2, 1:1, and 2:1 to obtain MAPA-1, MAPA-2, and MAPA-3, respectively. The three MAPAs were structurally characterized by proton nuclear magnetic resonance (H NMR) and Fourier transform infrared (FTIR) spectroscopic methods. 5-μm-thick dentin films were microtomed from dentin slabs of third molars. Following demineralization, films or slabs were treated with 1% MAPAs or PA in ethanol for 30 s. Collagen bio-stabilization against enzymatic degradation was analyzed by weight loss (WL) and hydroxyproline release (HYP) of films, as well as scanning electron microscopy (SEM) on dentin slabs. Crosslinking capacity and interactions of MAPAs with collagen were investigated by FTIR. Data were analyzed by ANOVA and Tukey's test (α = 0.05%).

Results: MA:PA feeding ratios affected MAPAs' chemical structures which in turn led to different collagen stabilization efficacy against degradation and varied collagen crosslinking capabilities. Higher collagen stabilization efficacy was detected using MAPA-1 (WL 10.52%; HYP 13.53 μg/mg) and MAPA-2 (WL 5.99%; HYP 11.02 μg/mg), which was comparable to that using PA (WL 8.79%; HYP 13.17 μg/mg) (p > 0.05), while a lower collagen stability occurred in MAPA-3 (WL 38.48%; HYP 29.49 μg/mg), indicating excessive MA-functionalization would compromise its stabilization efficacy. In comparison, complete digestion was detected for untreated collagen (WL 100%; HYP 102.76 μg/mg). The above results were consistent with collagen crosslinking efficacy of the three MAPAs revealed by SEM and FTIR.

Significance: A new class of novel polymerizable collagen cross-linkers MAPAs was synthesized and shown that, when appropriate MA:PA ratios were applied, the resulting MAPAs could render high collagen stability and the ability to copolymerize with resin monomers, overcoming the drawbacks of PA. These new polymerizable crosslinkers, when included in adhesives, could lead to long-lasting dentin bonding.
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http://dx.doi.org/10.1016/j.dental.2021.04.006DOI Listing
May 2021

Inactivation of TOPK Caused by Hyperglycemia Blocks Diabetic Heart Sensitivity to Sevoflurane Postconditioning by Impairing the PTEN/PI3K/Akt Signaling.

Oxid Med Cell Longev 2021 23;2021:6657529. Epub 2021 Apr 23.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

The cardioprotective effect of sevoflurane postconditioning (SPostC) is lost in diabetes that is associated with cardiac phosphatase and tensin homologue on chromosome 10 (PTEN) activation and phosphoinositide 3-kinase (PI3K)/Akt inactivation. T-LAK cell-originated protein kinase (TOPK), a mitogen-activated protein kinase- (MAPKK-) like serine/threonine kinase, has been shown to inactivate PTEN (phosphorylated status), which in turn activates the PI3K/Akt signaling (phosphorylated status). However, the functions of TOPK and molecular mechanism underlying SPostC cardioprotection in nondiabetes but not in diabetes remain unknown. We presumed that SPostC exerts cardioprotective effects by activating PTEN/PI3K/Akt through TOPK in nondiabetes and that impairment of TOPK/PTEN/Akt blocks diabetic heart sensitivity to SPostC. We found that in the nondiabetic C57BL/6 mice, SPostC significantly attenuated postischemic infarct size, oxidative stress, and myocardial apoptosis that was accompanied with enhanced p-TOPK, p-PTEN, and p-Akt. These beneficial effects of SPostC were abolished by either TOPK kinase inhibitor HI-TOPK-032 or PI3K/Akt inhibitor LY294002. Similarly, SPostC remarkably attenuated hypoxia/reoxygenation-induced cardiomyocyte damage and oxidative stress accompanied with increased p-TOPK, p-PTEN, and p-Akt in H9c2 cells exposed to normal glucose, which were canceled by either TOPK inhibition or Akt inhibition. However, either in streptozotocin-induced diabetic mice or in H9c2 cells exposed to high glucose, the cardioprotective effect of SPostC was canceled, accompanied by increased oxidative stress, decreased TOPK phosphorylation, and impaired PTEN/PI3K/Akt signaling. In addition, TOPK overexpression restored posthypoxic p-PTEN and p-Akt and decreased cell death and oxidative stress in H9c2 cells exposed to high glucose, which was blocked by PI3K/Akt inhibition. In summary, SPostC prevented myocardial ischemia/reperfusion injury possibly through TOPK-mediated PTEN/PI3K/Akt activation and impaired activation of this signaling pathway may be responsible for the loss of SPostC cardioprotection by SPostC in diabetes.
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http://dx.doi.org/10.1155/2021/6657529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093075PMC
May 2021

Prostaglandin E attenuates macrophage-associated inflammation and prostate tumour growth by modulating polarization.

J Cell Mol Med 2021 Jun 13;25(12):5586-5601. Epub 2021 May 13.

Wuxi School of Medicine, Jiangnan University, Wuxi, China.

Alternative polarization of macrophages regulates multiple biological processes. While M1-polarized macrophages generally mediate rapid immune responses, M2-polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)-derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E (PGE ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE played an anti-inflammatory role by inhibiting LPS and interferon-γ-induced M1 polarization and promoting interleukin-4-mediated M2 polarization (M2a). Further, we found that although PGE had no direct effect on the growth of prostate cancer cells in vitro, PGE could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE significantly inhibited prostate cancer cell growth in a cancer cell-macrophage co-culture system. Experimental results showed that PGE inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate cancer.
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http://dx.doi.org/10.1111/jcmm.16570DOI Listing
June 2021

Impairments in brain perfusion, executive control network, topological characteristics, and neurocognition in adult patients with asymptomatic Moyamoya disease.

BMC Neurosci 2021 May 12;22(1):35. Epub 2021 May 12.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China.

Background: Asymptomatic Moyamoya disease (MMD) impairs hemodynamic and cognitive function. The relationship between these changes, cerebral blood flow (CBF), and network connectivity remains largely unknown. The aim of this study was to increase understanding of the relationship between CBF, functional networks, and neurocognition in adults with asymptomatic MMD. We compared CBF and functional status in 26 patients with MMD and 20 healthy controls using arterial spin labeling and resting state functional magnetic resonance imaging sequences. At the same time, a detailed cognitive test was performed in 15 patients with no cerebral or lumen infarction who were selected by magnetic resonance imaging-T2 FLAIR screening.

Results: Compared to the controls, the patients showed varying degrees of decline in their computational ability (simple subtraction, p = 0.009; complex subtraction, p = 0.006) and short-term memory (p = 0.042). The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island flap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group.

Conclusions: In patients with asymptomatic MMD, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline and appear before clinical symptoms. Clinical trial registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR1900023610.
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http://dx.doi.org/10.1186/s12868-021-00638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117595PMC
May 2021

Clinical application of NRS-2002 in nutritional risk screening of tuberculosis inpatients.

Ann Palliat Med 2021 May 12;10(5):5322-5328. Epub 2021 May 12.

Department of Infectious Diseases, Suining Central Hospital, Suining, China.

Background: Tuberculosis (TB) is an infectious disease with high incidence and morbidity, which threatens the health of people. This study aims to investigate the nutritional risk status of TB inpatients and its correlation with disease prognosis.

Methods: A total of 295 patients with TB hospitalized in Suining Central Hospital from January 1, 2018 to June 30, 2018 were assessed by nutritional risk screening 2002 system within 2 days of admission. According to their assessment score, patients were divided into two groups: the nutritional risk group and the non-nutritional risk group. The differences in age, gender, TB classification, comorbid diseases, body mass index, serum albumin, complications, and the length of hospital stay were analyzed between the two groups.

Results: In the study population, 64.41% of TB inpatients were assessed as being at nutritional risk. There were significant differences in age, combined diseases, body mass index, serum albumin, incidence of complications, and length of hospital stay between the nutritional risk group and the non-nutritional risk group (P<0.05).

Conclusions: TB inpatients are often at nutritional risk, and the incidence of complications in patients with nutritional risk is high and the hospital stay prolongs. The nutritional status of TB inpatients is also related to the progression and prognosis of the disease.
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http://dx.doi.org/10.21037/apm-21-610DOI Listing
May 2021

Distinctive roles of fibrillar collagen I and collagen III in mediating fibroblast-matrix interaction: A nanoscopic study.

Biochem Biophys Res Commun 2021 Jun 8;560:66-71. Epub 2021 May 8.

Department of Chemistry, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL, 60616, USA. Electronic address:

One major goal in tissue engineering is to create functional materials, mimicking scaffolds in native tissues, to modulate cell function for tissue repair. Collagen is the most abundant structural protein in human body. Though collagen I (COLI) and collagen III (COLIII) are the predominant collagen types in connective tissues and they form stable hybrid fibrils at varied ratios, cell responses to the hybrid matrices are underinvestigated. In this work, we aim to explicate the distinctive roles of COLI and COLIII in fibroblast activation. Unidirectionally aligned COLI, COLIII and COLI-COLIII hybrid nanofibrils were generated via epitaxial growth of collagen on mica. AFM analyses revealed that, with the increase of COLI/COLIII ratio, the fibril width and stiffness increased and the binding affinity of cells to the matrix decreased. A hybrid matrix was found to activate fibroblasts the most effectively, characterized by extensive cell polarization with rigid stress fiber bundles and high α-SMA expression, and by the highest-level of collagen synthesis. It is ascribed to the fine balance between biochemical and biophysical cues achieved on the hybrid matrix. Thus, matrices of aligned COLI-COLIII hybrid fibrils and their derived multifunctional composites can be good candidates of implantation scaffolds for tissue regeneration.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165026PMC
June 2021

Methacrylate-functionalized proanthocyanidins as novel polymerizable collagen cross-linkers - Part 2: Effects on polymerization, microhardness and leaching of adhesives.

Dent Mater 2021 May 5. Epub 2021 May 5.

School of Dentistry, University of Missouri - Kansas City, Kansas City, MO, 64108, USA. Electronic address:

Objective: The aim of the study was to investigate the effects of a novel polymerizable collagen cross-linker methacrylate-functionalized proanthocyanidins (MAPA) on the polymerization, microhardness and leaching of a HEMA-based experimental dental adhesive system.

Methods: Three MAPAs were synthesized using different methacrylate (MA) to proanthocyanidins (PA) feeding ratios of 1:2, 1:1, and 2:1 to obtain MAPA-1, MAPA-2, and MAPA-3, respectively. The resulting three MAPAs and PA were added to an experimental adhesive formulated with HEMA and a tri-component photoinitiator system (0.5 wt% CQ/EDMAB/DPIHP) at 1%, 5% and 10% MAPA or PA concentrations (wt%). The adhesive polymerization kinetics was measured continuously in real-time for 10 min using a Fourier-transform infrared spectroscopy (FTIR) with an attenuated total reflectance (ATR) accessory. Degree of conversion (DC) and Vickers microhardness (MH) of cured adhesives were measured at 72 h post-cure. The leaching of cured adhesives in DI water was monitored using UV-vis spectrophotometer. Statistical analysis was performed using one-way and two-way ANOVA, Tukey's (p < 0.05).

Results: The adhesive formulations with 1%, 5% and 10% MAPAs-1, -2, -3 all generated higher rate of polymerization and 10-min DC than the formulations with PA at the same concentrations. At 72 h post-cure, the adhesive formulation with 5% MAPA-2 exhibited significantly higher DC (99.40%) and more than doubled MH (18.93) values than the formulation with 5% PA (DC = 89.47%, MH = 8.41) and the control (DC = 95.46%, MH = 9.33). Moreover, the cured adhesive with 5% MAPA-2 demonstrated significantly reduced PA leaching in comparison with cured adhesive with 5% PA.

Significance: Synthesized MAPA is a novel class of polymerizable collagen cross-linker that not only stabilizes dentin collagen via its PA component, but also improves polymerization, mechanical properties and stability of HEMA-based adhesives via its MA component. By inheriting the benefit while overcoming the drawback of PA, MAPA offers a revolutionary solution for improved bond-strength and longevity of dental restorations.
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http://dx.doi.org/10.1016/j.dental.2021.04.010DOI Listing
May 2021

Three-Dimensional-Printable Thermo/Photo-Cross-Linked Methacrylated Chitosan-Gelatin Hydrogel Composites for Tissue Engineering.

ACS Appl Mater Interfaces 2021 May 7;13(19):22902-22913. Epub 2021 May 7.

Physik-Department, Lehrstuhl für Funktionelle Materialien, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany.

Biomimetic constructs imitating the functions, structures, and compositions of normal tissues are of great importance for tissue repair and regeneration. Three-dimensional (3D) printing is an innovative method to construct intricate biomimetic 3D tissue engineering scaffolds with spatiotemporal deposition of materials to control the intrinsic architectural organization and functional performance of the scaffold. However, due to the lack of bioinks with suitable printability, high structural integrity, and biological compatibility, producing constructs that mimic the anisotropic 3D extracellular environments remains a challenge. Here, we present a printable hydrogel ink based on methylacrylate-modified chitosan (ChMA) and gelatin (GelMA) embedding nanohydroxyapatite (nano-Hap). This polymer composite is first physically cross-linked by thermal gelation for postprinting structural stability, followed by covalent photo-cross-linking of ChMA and GelMA to form a long-term stable structure. The rheological behavior of the hydrogels and the mechanical strengths of the printed constructs are tuned by adjusting the content of GelMA, which in turn enhances the shape retention after printing and enables the precise deposition of multilayered 3D scaffolds. Moreover, the formulated biomaterial inks exhibit biological characteristics that effectively support the spreading and proliferation of stem cells seeded on the scaffolds after 7 days of in vitro culture. Adding Hap has minor influences on the mechanical rigidity and cytocompatibility of the hydrogels compared with the group free of Hap. Together, the printable biomaterial inks with shear thinning and good structural integrity, along with biological cues, are promising for tissue engineering application.
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http://dx.doi.org/10.1021/acsami.1c01321DOI Listing
May 2021