Publications by authors named "Hong Wu"

1,539 Publications

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Near-Infrared Spectroscopy Monitoring of Cerebral Oxygenation and Influencing Factors in Neonates from High-Altitude Areas.

Neonatology 2021 Jun 9:1-6. Epub 2021 Jun 9.

Pediatric Department, Peking University First Hospital, Beijing, China.

Background: Accurate detection of cerebral oxygen saturation (rSO2) may be useful for neonatal brain injury prevention, and the normal range of rSO2 of neonates at high altitude remained unclear.

Objective: To compare cerebral rSO2 and cerebral fractional tissue oxygen extraction (cFTOE) at high-altitude and low-altitude areas in healthy neonates and neonates with underlying diseases.

Methods: 515 neonates from low-altitude areas and 151 from Tibet were enrolled. These neonates were assigned into the normal group, hypoxic-ischemic encephalopathy (HIE) group, and other diseases group. Near-infrared spectroscopy was used to measure rSO2 in neonates within 24 h after admission. The differences of rSO2, pulse oxygen saturation (SpO2), and cFTOE levels were compared between neonates from low- and high-altitude areas.

Results: (1) The mean rSO2 and cFTOE levels in normal neonates from Tibet were 55.0 ± 6.4% and 32.6 ± 8.5%, significantly lower than those from low-altitude areas (p < 0.05). (2) At high altitude, neonates with HIE, pneumonia (p < 0.05), anemia, and congenital heart disease (p < 0.05) have higher cFTOE than healthy neonates. (3) Compared with HIE neonates from plain areas, neonates with HIE at higher altitude had lower cFTOE (p < 0.05), while neonates with heart disease in plateau areas had higher cFTOE than those in plain areas (p < 0.05).

Conclusions: The rSO2 and cFTOE levels in normal neonates from high-altitude areas are lower than neonates from the low-altitude areas. Lower cFTOE is possibly because of an increase in blood flow to the brain, and this may be adversely affected by disease states which may increase the risk of brain injury.
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http://dx.doi.org/10.1159/000514403DOI Listing
June 2021

The Value of Blood Urea Nitrogen in the Prediction of Risks of Cardiovascular Disease in an Older Population.

Front Cardiovasc Med 2021 20;8:614117. Epub 2021 May 20.

Shanghai East Hospital, Tongji University, Shanghai, China.

High blood urea nitrogen (BUN) is associated with adverse outcomes in patients with cardiac disease risks. However, no study has explored whether BUN can predict the risk of cardiovascular disease (CVD) in the healthy older population. This study aims to explore the incidence and risk factors of CVD among a healthy older population community in China. This study was designed as a cohort study with a 4-year follow-up. We recruited 5,000 older people among 137,625 residents of the Gaohang community. In the baseline, subjects were asked to participate in medical screening and biological tests, and answered survey questions. During the follow-up period (2014-2017), the researchers regularly tested the subjects' indicators and assessment scales. We monitored the occurrence of CVD and explored the relationship between BUN and CVD via a Cox regression analysis. During the follow-up, subjects were newly diagnosed with CVD including heart failure (HF), heart disease events, atrial fibrillation, diabetes, hypertension, metabolic syndrome, and kidney disease. The Cox regression analysis found an association between baseline BUN and incident CVD in female subjects, with higher BUN associated with increased risk of AF in females and kidney disease in both male and females. No association was found between BUN and CVD in male subjects. Current results indicate that BUN is a valuable predictive biomarker of CVD. A higher BUN level (>13.51 mg/dL) is associated with an increased occurrence of HF but a decreased occurrence of diabetes and metabolic symptoms in normal older females.
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http://dx.doi.org/10.3389/fcvm.2021.614117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173137PMC
May 2021

Gold-iron selenide nanocomposites for amplified tumor oxidative stress-augmented photo-radiotherapy.

Biomater Sci 2021 Jun;9(11):3979-3988

Key Laboratory of Advanced Materials, Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. and State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

The radio-resistance of tumor tissues has been considered a great challenge for cancer radiotherapy (RT).The development of nanoparticle (NP)-based radio-sensitizers can enhance the radio-sensitization of tumor tissues while reducing the side effects to surrounding tissues. However, most of the nano-radiosensitizers show increased radiation deposition with a high-Z element but achieve limited enhancement. Herein, we investigated polyethylene glycol (PEG)-modified gold-iron selenide nanocomposites (Au-FeSe2 NCs) for simultaneously enhancing therapeutic effects in multiple ways. In this study, the high-Z element Au (Z = 79) endows Au-FeSe2 NCs with enhanced X-ray deposition and thus causes more DNA damage. On the other hand, Au-FeSe2 exhibits the ability to produce reactive oxygen species (ROS) by catalyzing endogenous hydrogen peroxide in tumor sites as well as improve the hydrogen peroxide level during ionizing irradiation. Finally, combined with photothermal therapy (PTT), Au-FeSe2 NCs could exhibit a remarkable RT/PTT synergistic effect on tumor treatment.
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http://dx.doi.org/10.1039/d1bm00306bDOI Listing
June 2021

Tight covalent organic framework membranes for efficient anion transport via molecular precursor engineering.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Tianjin University, School of Chemical Engineering and Technology, Weijin Road, 300072, Tianjin, CHINA.

Fabricating covalent organic frameworks (COFs) membranes with tight structure, which can fully utilize well-defined framework structure and thus achieve superior conduction performance, remains a grand challenge. Herein, through molecular precursor engineering of COFs, we reported the fabrication of tight COFs membrane with the ever-reported highest hydroxide ion conductivity over 200 mS cm-1 at 80 °C, 100% RH. Six quaternary ammonium-functionalized COFs were synthesized by assembling functional hydrazides and different aldehyde precursors. In an organic-aqueous reaction system, the impact of the aldehyde precursors with different size, electrophilicity and hydrophilicity on the reaction-diffusion process for fabricating COFs membranes was elucidated. Particularly, more hydrophilic aldehydes were prone to push the reaction zone from the interface region to the aqueous phase of the reaction system, the tight membranes were thus fabricated via phase-transfer polymerization process, conferring around 4~8 times the anion conductivity over the loose membranes via interfacial polymerization process.
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http://dx.doi.org/10.1002/anie.202105190DOI Listing
June 2021

Scalable fabrication of crystalline COF membrane from amorphous polymeric membrane.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Tianjin University, School of Chemical Engineering and Technology, Weijin Road, 300072, Tianjin, CHINA.

Covalent organic framework (COF) membranes hold tremendous potential for widespread applicability, but their scalable fabrication remains challenging. Here, we demonstrate the disorder-to-order transformation from amorphous polymeric membrane to crystalline COF membrane via monomer exchange. Solution-processing method is used to prepare amorphous membranes and the replacing monomer is selected based on the chemical and thermodynamical stability of the final framework. Afterwards, the reversible imine bonds allow the extraneous monomers to replace the pristine monomers within amorphous membrane, driving the transformation from disordered network to ordered framework. The incorporation of intramolecular hydrogen bonds enables the crystalline COF to imprint the morphology of amorphous membrane. The COF membranes harvest proton conductivity up to 0.53 S cm -1 at 80 °C. Our strategy builds a bridge between amorphous polymeric and crystalline COF membranes, not only paving the way to large-scale fabrication of COF membranes, but also affording some guidance on materials processing via disorder-to-order transformation.
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http://dx.doi.org/10.1002/anie.202102965DOI Listing
June 2021

A Guideline-Based Decision Tree Achieves Better Glucose Control with Less Hypoglycemia at 3 Months in Chinese Diabetic Patients.

Diabetes Ther 2021 May 29. Epub 2021 May 29.

Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.

Introduction: China has the world's largest diabetes epidemic and has been facing a serious shortage of primary care providers for chronic diseases including diabetes. To help primary care physicians follow guidelines and mitigate the workload in primary care communities in China, we developed a guideline-based decision tree. This study aimed to validate it at 3 months with real-world data.

Methods: The decision tree was developed based on the 2017 Chinese Type 2 Diabetes (T2DM) guideline and 2018 guideline for primary care. It was validated with the data from two registry studies: the NEW2D and ORBIT studies. Patients' data were divided into two groups: the compliance and non-compliance group, depending on whether the physician's prescription was consistent with the decision tree or not. The primary outcome was the difference of change in HbA1c from baseline to 3 months between the two groups. The secondary outcomes included the difference in the proportion of patients achieving HbA1c < 7% at 3 months between the two groups, the incidence of self-reported hypoglycemia at 3 months, and the proportion of patients (baseline HbA1c ≥ 7%) with a HbA1c reduction ≥ 0.3%. The statistical analysis was performed using linear or logistic regression with inverse probability of treatment weighting with adjustments of confounding factors.

Results: There was a 0.9% reduction of HbA1c in the compliance group and a 0.8% reduction in the non-compliance group (P < 0.001); 61.1% of the participants in the compliance group and 44.3% of the participants in the non-compliance group achieved a HbA1c level < 7% at 3 months (P < 0.001). The hypoglycemic events occurred in 7.1% of patients in the compliance group vs. 9.4% in the non-compliance group (P < 0.001).

Conclusion: The decision tree can help physicians to treat their patients so that they achieve their glycemic targets with fewer hypoglycemic risks. ( http://www.clinicaltrials.gov NCT01525693 & NCT01859598).
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http://dx.doi.org/10.1007/s13300-021-01075-1DOI Listing
May 2021

Successful management of the hepatocellular carcinoma with inferior vena cava tumor thrombus: A case report.

Medicine (Baltimore) 2021 May;100(21):e26081

Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy.

Rationale: Hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT) is traditionally considered an advanced-stage cancer with a poor prognosis. There is no standard treatment for patients diagnosed as HCC with IVCTT.

Patient Concerns: A 52-year-old man was admitted to our hospital because of suspected hepatic mass during a health examination.

Diagnoses: Computed tomography (CT) showed a hepatic mass approximately 4.3 cm × 6.3 cm in size located in segment VII of the liver, with thrombus in the inferior vena cava. The mass exhibited a pattern of early enhancement and washout on contrast-enhanced CT. Alpha-fetoprotein was 614.1 ng/mL (normal value, <8 ng/mL). The preoperative diagnosis was HCC with IVCTT.

Interventions: Two months after stereotactic body radiotherapy combined with sorafenib therapy, a planned open anatomical resection of the right posterior lobe of the liver was performed.

Outcomes: The patient is alive without disease 12 months after surgery, and the level of alpha-fetoprotein is normal.

Lessons: The patient diagnosed as HCC with IVCTT was successfully treated by stereotactic body radiotherapy combined with molecularly targeted drugs followed by surgical treatment. If confirmed in future studies, this would suggest a promising strategy for the management of HCC with IVCTT.
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http://dx.doi.org/10.1097/MD.0000000000026081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154412PMC
May 2021

The response of macrophages and their osteogenic potential modulated by micro/nano-structured Ti surfaces.

Colloids Surf B Biointerfaces 2021 May 13;205:111848. Epub 2021 May 13.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, PR China. Electronic address:

Current understanding on the interactions between micro/nano-structured Ti surfaces and macrophages is still limited. In this work, TiO nano-structures were introduced onto acid-etched Ti surfaces by alkali-heat treatment, ion exchange and subsequent heat treatment. By adjusting the concentration of NaOH during alkali-heat treatment, nano-flakes, nano-flakes mixed with nano-wires or nano-wires could formed on acid-etched Ti surfaces. The micro- and micro/nano-structured Ti surfaces possessed similar surface chemical and phase compositions. In vitro results indicate that the morphology of macrophages was highly dependent on the morphological features of nano-structures. Nano-flakes and nano-wires were favorable to induce the formation of lamellipodia and filopodia, respectively. Compared to micro-structured Ti surface, micro/nano-structured Ti surfaces polarized macrophages to their M2 phenotype and enhanced the gene expressions of osteogenic growth factors in macrophages. The M2 polarized macrophages promoted the maturation of osteoblasts. Compared to that with nano-flakes or nano-wires, the surface with mixed features of nano-flakes and nano-wires exhibited stronger anti-inflammatory and osteo-immunomodulatory effects. The findings presented in the current work suggest that introducing micro/nano-topographies onto Ti-based implant surfaces is a promising strategy to modulate the inflammatory response and mediate osteogenesis.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111848DOI Listing
May 2021

The Transcriptomic Landscape of Mismatch Repair-Deficient Intestinal Stem Cells.

Cancer Res 2021 May 18;81(10):2760-2773. Epub 2021 Mar 18.

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Lynch syndrome is the most common cause of hereditary colorectal cancer and is secondary to germline alterations in one of four DNA mismatch repair (MMR) genes. Here we aimed to provide novel insights into the initiation of MMR-deficient (MMRd) colorectal carcinogenesis by characterizing the expression profile of MMRd intestinal stem cells (ISC). A tissue-specific MMRd mouse model (Villin-Cre;Msh2 ) was crossed with a reporter mouse () to trace and isolate ISCs (Lgr5+) using flow cytometry. Three different ISC genotypes (-KO, -HET, and -WT) were isolated and processed for mRNA-seq and mass spectrometry, followed by bioinformatic analyses to identify expression signatures of complete MMRd and haplo-insufficiency. These findings were validated using qRT-PCR, IHC, and whole transcriptomic sequencing in mouse tissues, organoids, and a cohort of human samples, including normal colorectal mucosa, premalignant lesions, and early-stage colorectal cancers from patients with Lynch syndrome and patients with familial adenomatous polyposis (FAP) as controls. -KO ISCs clustered together with differentiated intestinal epithelial cells from all genotypes. Gene-set enrichment analysis indicated inhibition of replication, cell-cycle progression, and the Wnt pathway and activation of epithelial signaling and immune reaction. An expression signature derived from MMRd ISCs successfully distinguished MMRd neoplastic lesions of patients with Lynch syndrome from FAP controls. SPP1 was specifically upregulated in MMRd ISCs and colocalized with LGR5 in Lynch syndrome colorectal premalignant lesions and tumors. These results show that expression signatures of MMRd ISC recapitulate the initial steps of Lynch syndrome carcinogenesis and have the potential to unveil novel biomarkers of early cancer initiation. SIGNIFICANCE: The transcriptomic and proteomic profile of MMR-deficient intestinal stem cells displays a unique set of genes with potential roles as biomarkers of cancer initiation and early progression.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2896DOI Listing
May 2021

Analysis of the influencing factors and nursing strategy for acute atelectasis after traumatic brain injury surgery.

Ann Palliat Med 2021 May 10;10(5):5425-5432. Epub 2021 May 10.

Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Acute atelectasis is common after traumatic brain injury (TBI), but the related factors and treatment are still unclear. This study is to analyze the independent risk factors for acute atelectasis after TBI and propose an interventional nursing strategy, in order to correct respiratory function and improve the prognosis of patients.

Methods: The clinical data of 93 patients with TBI admitted to our hospital from April 2015 to October 2019 were retrospectively analyzed. Clinical data were analyzed by single factor analysis, the cutoff value of influencing factors was obtained by receiver operating characteristic (ROC) curve analysis, and the influencing factors for acute atelectasis after TBI were examined by multi-factor logistic regression.

Results: Twenty-two patients (23.66%) were complicated with acute atelectasis during the observation period, while the remaining 71 patients (76.34%) did not have acute atelectasis. Univariate analysis showed that there were significant differences in the Glasgow Coma Scale (GCS), history of vomiting and aspiration, mannitol use, mechanical ventilation, hypoalbuminemia, and serum hypoxia-inducible factor-1α (HIF-1α) between the acute atelectasis group and the non-acute atelectasis group (P<0.05). The AUC area of HIF-1α level predicting acute atelectasis was 0.896 [95% confidence interval (CI): 0.814-0.978, P=0.042], and the cut-off value was 2.12 mmol/L, with a sensitivity of 76.9% and a specificity of 93.3%. Logistic regression analysis showed that a history of vomiting and aspiration [odds ratio (OR) 3.908, 95% confidence interval (CI): 1.201-12.712], mechanical ventilation (OR 3.250, 95% CI: 1.139-9.271), hypoalbuminemia (OR 5.741, 95% Cl: 1.926-17.113), and HIF-1α ≥2.12 mmol/L (OR 6.623, 95% CI: 2.364-16.346) were independent risk factors for acute atelectasis after TBI.

Conclusions: A history of vomiting and aspiration, mechanical ventilation, hypoalbuminemia, and high expression of HIF-1α are all independent risk factors for postoperative acute atelectasis in patients with TBI. In clinical practice, patients should be guided to swallow properly, breathe smoothly, eat well, and regularly check the relevant indexes.
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http://dx.doi.org/10.21037/apm-21-790DOI Listing
May 2021

Gene expression signatures differentiating major depressive disorder from subsyndromal symptomatic depression.

Aging (Albany NY) 2021 05 8;13(9):13124-13137. Epub 2021 May 8.

Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Subsyndromal symptomatic depression (SSD) and major depressive disorder (MDD) have been classified as distinct diseases, due to their dissimilar gene expression profiles and responses to venlafaxine. To identify specific biomarkers of these two diseases, we conducted a secondary analysis of the gene expression signatures of SSD patients, MDD patients and healthy controls (n=8/group) from the study of Yi et al. Global, individual, specific, enrichment and co-expression analyses were used to compare the transcriptomic profiles of peripheral blood lymphocytes from the three groups. The global and individual analyses revealed that different genes were up- and downregulated in the SSD and MDD groups. Through our specific analysis, we identified 1719 and 3278 differentially expressed genes specifically associated with MDD and SSD, respectively. Enrichment and co-expression analyses demonstrated that the genes specific to MDD were enriched in pathways associated with hormone levels and immune responses, while those specific to SSD were associated with immune function. The specific hub gene for the MDD co-expression network was transmembrane protein 132B (TMEM132B), while the hub genes for SSD were actin-related protein 2/3 complex (ARPC2) and solute carrier family 5 member 5 (SLC5A5). This bioinformatic analysis has provided potential biomarkers that can distinguish SSD from MDD.
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http://dx.doi.org/10.18632/aging.202995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148500PMC
May 2021

Optimizing the sulfonic groups of a polymer to coat the zinc anode for dendrite suppression.

Chem Commun (Camb) 2021 May;57(43):5326-5329

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. China.

The zinc metal anodes in aqueous zinc-ion batteries suffer from low cycling performance caused by uncontrolled dendrite. We have designed sulfonated poly-ether-ether-ketone (SPEEK) polymers as a surface coating layer on the zinc anode for dendrite suppression, in which the sulfonic groups in polymers act as effective active sites for zinc-ion diffusion. In SPEEK, the un-sulfonated domain serves as the framework and the sulfonated domain serves as the functional part to re-distribute the zinc ions. By optimizing the degree of SPEEK sulfonation, the best zinc anode coating has been achieved to present a high reversibility of over 1600 hours in symmetric cells and improved performance in full cells.
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http://dx.doi.org/10.1039/d1cc00924aDOI Listing
May 2021

Fabrication of Nano/Micro-Structured Electrospun Detection Card for the Detection of Pesticide Residues.

Foods 2021 Apr 19;10(4). Epub 2021 Apr 19.

College of Biosciences and Bioengineering, South China University of Technology, Guangzhou 510640, China.

A novel nano/micro-structured pesticide detection card was developed by combining electrospinning and hydrophilic modification, and its feasibility for detecting different pesticides was investigated. Here, the plain and hydrophilic-modified poly(ε-caprolactone) (PCL) fiber mats were used for the absorption of indolyl acetate and acetylcholinesterase (AChE), respectively. By pre-treating the fiber mat with ethanol, its surface wettability was improved, thus, promoting the hydrolysis of the PCL fiber mat. Furthermore, the absorption efficiency of AChE was improved by almost two times due to the increased hydrophilicity of the modified fiber mat. Noteworthily, this self-made detection card showed a 5-fold, 2-fold, and 1.5-fold reduction of the minimum detectable concentration for carbofuran, malathion, and trichlorfon, respectively, compared to the national standard values. Additionally, it also exhibited good stability when stored at 4 °C and room temperature. The food detection test showed that this nano/micro-based detection card had better detectability than the commercial detection card. Therefore, this study offers new insights into the design of pesticide detection cards, which also broadens the application of electrospinning technique.
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http://dx.doi.org/10.3390/foods10040889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073816PMC
April 2021

Tannic acid-based metal phenolic networks for bio-applications: a review.

J Mater Chem B 2021 05;9(20):4098-4110

Key Laboratory of Advanced Materials, Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. and State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

Tannic acid (TA), a large polyphenolic molecule, has long been known for use in food additives, antioxidants, bio-sorbents, animal feed and adhesives due to its intrinsic properties such as antioxidation, metal chelation, and polymerization. Recently, there has been a renewed interest in fabricating engineered advanced materials with TA modification for novel bio-applications. The modification process involves various interactions/reactions based on its diverse chemical structure, contributed by abundant aromatic rings and hydroxyl groups. In addition, the obtained composites are endowed with retained TA activity and novel enhanced properties. Therefore, the aim of this review is to highlight the recent biomedical application of TA-based metal phenolic networks (TA-MPNs) by focusing on their intrinsic properties and the endowed ability for novel engineered functional composites. The potential contributions of TA-MPNs in "Tumor Theranostics", "Anti-Bacterial Ability", "Wound Repair for Skin Regeneration" and "Bone Tissue Regeneration Applications" are summarized in this paper.
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http://dx.doi.org/10.1039/d1tb00383fDOI Listing
May 2021

MiR-326 mediates malignant biological behaviors of lung adenocarcinoma by targeting ZEB1.

Sci Prog 2021 Apr-Jun;104(2):368504211009379

School of medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

MiR-326 functions as an antioncogene in the several types of cancer. However, the underling mechanisms through which miRNA-326 regulates the anti-carcinogenesis of lung adenocarcinoma have remained elusive. The aim of this study was to explore the role and regulatory mechanism of miR-326 in cell proliferation, invasion, migration and apoptosis in lung adenocarcinoma. Quantitative real-time PCR (qRT-PCR) was used to detect the expression pattern of miR-326 in human bronchial epithelial cells (HBES-2B), 4 kinds of lung adenocarcinoma cell lines (H23, H1975, H2228, H2085) and 20 lung adenocarcinoma tissues. Then, H23 cells were infected with miR-326 mimics, miR-326 inhibitors and si-ZEB1 to build up-regulated miR-326 cell lines, down-regulated ZEB1(zinc-finger-enhancer binding protein 1)cell lines, simultaneous down-regulated ZEB1 and miR-326 cell lines. Moreover, CCK-8 assay, transwell invasion assay, wound healing assay and flow cytometry assay were employed to examine the effects of miR-326 and ZEB1 on the proliferation, invasion, migration and apoptosis abilities of H23 cells. Western blot was performed to explore the effects of miR-326 and ZEB1 on the expression of invasion and migration related proteins N-cadherin, E-cadherin, MMP7, MMP13, SLUG and apoptotic proteins PARP, BAX. On the mechanism, a dual-luciferase reporter gene was used to measure the target relationship between miR-326 and ZEB1. MiR-326 expression was significantly downregulated in lung adenocarcinoma tissues and cells. Overexpression of miR-326 significantly inhibited the malignant behaviors of H23 cells. Mechanically, luciferase reporter assay showed that ZEB1 was a direct target of miR-326. MiR-326 mimic downregulated the expression of ZEB1. Furthermore, knocking down ZEB1 strongly inhibited the proliferation, invasion and migration of H23 cells but promoted apoptosis. MiR-326 could target ZEB1 to inhibit the proliferation, invasion and migration of lung adenocarcinoma cells and promote apoptosis, which is a potential therapeutic target for lung adenocarcinoma.
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http://dx.doi.org/10.1177/00368504211009379DOI Listing
April 2021

The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure.

J Transl Med 2021 04 28;19(1):176. Epub 2021 Apr 28.

Department of Reproductive Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, Hunan, China.

Background: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF.

Methods: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group.

Results: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts.

Conclusions: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.
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http://dx.doi.org/10.1186/s12967-021-02837-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082865PMC
April 2021

The SiTian Project.

An Acad Bras Cienc 2021 23;93(suppl 1):e20200628. Epub 2021 Apr 23.

National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Rd, Chaoyang 100101, Beijing, China.

SiTian is an ambitious ground-based all-sky optical monitoring project, developed by the Chinese Academy of Sciences. The concept is an integrated network of dozens of 1-m-class telescopes deployed partly in China and partly at various other sites around the world. The main science goals are the detection, identification and monitoring of optical transients (such as gravitational wave events, fast radio bursts, supernovae) on the largely unknown timescales of less than 1 day; SiTian will also provide a treasure trove of data for studies of AGN, quasars, variable stars, planets, asteroids, and microlensing events. To achieve those goals, SiTian will scan at least 10,000 square deg of sky every 30 min, down to a detection limit of $V \approx 21$ mag. The scans will produce simultaneous light-curves in 3 optical bands. In addition, SiTian will include at least three 4-m telescopes specifically allocated for follow-up spectroscopy of the most interesting targets. We plan to complete the installation of 72 telescopes by 2030 and start full scientific operations in 2032.
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http://dx.doi.org/10.1590/0001-3765202120200628DOI Listing
April 2021

Prediction of Prognosis for cHCC-CC Patients After Surgery: Comparison of Tumor Marker Score Based on AFP, CEA, CA19-9, and Other Clinical Stages.

Ann Surg Oncol 2021 Apr 26. Epub 2021 Apr 26.

Department of Liver Surgery and Liver Transplantation Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: The effectiveness of clinical stage as a prognostic factor in combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) patients is controversial.

Patients And Methods: Medical records of all pathologically confirmed cHCC-CC patients from 2000 to 2017 at West China Hospital were retrieved. Tumor marker score (TMS) was determined from optimal AFP, CEA, and CA19-9 cutoff values. Interaction and subgroup analysis were conducted according to potential confounders. Prognostic value of TMS and other prognostic models were evaluated by Kaplan-Meier (K-M) analysis, c-index, and time-dependent receiver operating curves (td-ROC).

Results: Optimal cutoff values for preoperative AFP, CEA, and CA19-9 were 10.76 ng/mL, 5.24 ng/mL, and 31.54 U/mL, respectively. Among 128 patients, 24, 58, and 46 were classified into TMS 0, TMS 1, and TMS ≥ 2, respectively. TMS could stratify our series into groups of statistically different prognosis. Subgroup analysis according to potential confounders and test for interactions showed that TMS 1 and TMS ≥ 2 were stable risk factors relative to TMS 0. Univariate (HR: TMS1 = 2.30, p = 0.014; TMS ≥ 2 = 5.1, p < 0.001) and multivariate Cox regression analyses (HR: TMS1 = 1.72, p = 0.124; TMS ≥ 2 = 4.15, p < 0.001) identified TMS as an independent prognostic risk factor. TMS had good discrimination (c-index 0.666, 95% CI 0.619-0.714), and calibration plots revealed favorable consistency. Area under the curve (AUC) value of td-ROC for TMS and integrated AUC was higher than for other clinical stages at any month within 5 years postoperation.

Conclusion: TMS exhibited optimal prognostic value over other widely used clinical stages for cHCC-CC after surgery and may guide clinicians in prognostic prediction.
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http://dx.doi.org/10.1245/s10434-021-09949-1DOI Listing
April 2021

Electrostatic-modulated interfacial polymerization toward ultra-permselective nanofiltration membranes.

iScience 2021 Apr 26;24(4):102369. Epub 2021 Mar 26.

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Interfacial polymerization (IP) is a platform technology for ultrathin membranes. However, most efforts in regulating the IP process have been focused on short-range H-bond interaction, often leading to low-permselective membranes. Herein, we report an electrostatic-modulated interfacial polymerization (eIP) supercharged phosphate-rich substrates toward ultra-permselective polyamide membranes. Phytate, a natural strongly charged organophosphate, confers high-density long-range electrostatic attraction to aqueous monomers and affords tunable charge density by flexible metal-organophosphate coordination. The electrostatic attraction spatially enriches amine monomers and temporally decelerates their diffusion into organic phase to be polymerized with acyl chloride monomers, triggering membrane sealing and inhibiting membrane growth, thus generating polyamide membranes with reduced thickness and enhanced cross-linking. The optimized nearly 10-nm-thick and highly cross-linked polyamide membrane displays superior water permeance and ionic selectivity. This eIP approach is applicable to the majority of conventional IP processes and can be extended to fabricate a variety of advanced membranes from polymers, supermolecules, and organic framework materials.
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http://dx.doi.org/10.1016/j.isci.2021.102369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059057PMC
April 2021

Atomic-Scale Visualization and Quantification of Configurational Entropy in Relation to Thermal Conductivity: A Proof-of-Principle Study in -GeSbTe.

Adv Sci (Weinh) 2021 Apr 8;8(8):2002051. Epub 2021 Feb 8.

College of Physics and Center for Quantum Materials and Devices Institute of Advanced Interdisciplinary Studies Chongqing University Chongqing 401331 P. R. China.

It remains a daunting task to quantify the configurational entropy of a material from atom-revolved electron microscopy images and correlate the results with the material's lattice thermal conductivity, which strides across statics, dynamics, and thermal transport of crystal lattice over orders of magnitudes in length and time. Here, a proof-of-principle study of atomic-scale visualization and quantification of configurational entropy in relation to thermal conductivity in single crystalline trigonal GeSbTe (aka -GeSbTe) with native atomic site disorder is reported. A concerted effort of large -GeSbTe single crystal growth, in-lab developed analysis procedure of atomic column intensity, the visualization and quantification of configurational entropy including corresponding modulation, and thermal transport measurements enable an entropic "bottom-up" perspective to the lattice thermal conductivity of -GeSbTe. It is uncovered that the configurational entropy increases phonon scattering and reduces phonon mean free path as well as promotes anharmonicity, thereby giving rise to low lattice thermal conductivity and promising thermoelectric performance. The current study sheds lights on an atomic scale bottom-up configurational entropy design in diverse regimes of structural and functional materials research and applications.
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http://dx.doi.org/10.1002/advs.202002051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061353PMC
April 2021

Fus knockdown inhibits the profibrogenic effect of cardiac fibroblasts induced by angiotensin II through targeting Pax3 thereby regulating TGF-β1/Smad pathway.

Bioengineered 2021 Dec;12(1):1415-1425

Department of Cardiology, The People's Hospital, Chongqing, China.

The Angiotensin II/transforming growth factor-β1 (AngII/TGF-β1) signal axis is an important regulatory pathway for atrial fibrosis, which can contribute to atrial fibrillation (AF). Fused in sarcoma (FUS) was recently found to regulate cardiac diseases. This study aimed to investigate whether FUS could regulate AngII induced fibrosis and uncover the possible mechanisms. The expression of FUS in AF patients and AngII-induced cardiac fibroblasts was measured by RT-qPCR and western blot assays. Fus was silenced in cells using short hairpin RNA (shRNA), then cell proliferation, migration, collagen synthesis and TGF-β1/Smad signaling were detected by CCK-8, wound healing and western blot assays, respectively. The possible target for Fus was predicted by searching Starbase database and verified by RNA-binding protein immunoprecipitation (RIP) and RNA pull down. Cells were overexpressed with Pax3 in the presence of Fus silence and AngII stimulation, then the above cellular processes were further evaluated. Results showed that FUS was upregulated in AF patients and AngII-induced cardiac fibroblasts. Fus knockdown inhibited AngII-enhanced cell proliferation, migration, collagen synthesis and TGF-β1/Smad signaling activation. Furthermore, Fus functions as an RNA-binding protein to bind to Pax3 mRNA and positively regulate its expression. Further studies demonstrated that Pax3 overexpression canceled the above effects of Fus knockdown on cell proliferation, migration, collagen synthesis, and TGF-β1/Smad signaling activation in AngII-induced cells. In conclusion, Fus could target Pax3 to increase the pro-fibrotic effect of AngII in cardiac fibroblasts via activating TGF-β1/Smad signaling. Knockdown of Fus/Pax3 axis may provide a potential therapy for relieving AF.
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http://dx.doi.org/10.1080/21655979.2021.1918522DOI Listing
December 2021

Containment of rumor spread by selecting immune nodes in social networks.

Math Biosci Eng 2021 03;18(3):2614-2631

School of Information Engineering, Qujing Normal University, Qujing 655000, China.

With the popularity of online social network these have become important platforms for the spread of information. This not only includes correct and useful information, but also false information, and even rumors which could result in panic. Therefore, the containment of rumor spread in social networks is important. In this paper, we propose an effective method that involves selecting a set of nodes in (k, η)-cores and immunize these nodes for rumor containment. First, we study rumor influence propagation in social networks under the extended Independent Cascade (EIC) model, an extension of the classic Independent Cascade (IC) model. Then, we decompose a social network into subgraphs via core decomposition of uncertain graphs and compute the number of immune nodes in each subgraph. Further we greedily select nodes with the Maximum Marginal Covering Neighbors Set as immune nodes. Finally, we conduct experiments using real-world datasets to evaluate our method. Experimental results show the effectiveness of our method.
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http://dx.doi.org/10.3934/mbe.2021133DOI Listing
March 2021

Effect of Enzymatic Hydrolysis on the Zinc Binding Capacity and Gastrointestinal Stability of Peptides Derived From Pumpkin (.) Seeds.

Front Nutr 2021 31;8:647782. Epub 2021 Mar 31.

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

Zinc is a crucial micronutrient for maintaining body immune system and metabolism function. However, insufficient intake from diet may lead to zinc deficiency and impair normal body function. In addition, conventional zinc salts supplementation has the disadvantage of low bioavailability since the zinc ions may be easily chelated by dietary fiber or phytate commonly found in diets rich in plants, and form precipitates that cannot be absorbed. Therefore, the objective of the present study is to prepare pumpkin seed derived peptides and to evaluate the effect of structure and surface properties on the zinc binding behavior of the pumpkin seed protein hydrolysate (PSPH), as well as their gastrointestinal stability. Briefly, different PSPHs were prepared using enzymatic hydrolysis method with bromelain, papain, flavourzyme, alcalase, and pepsin. The particle size, zeta potential, surface hydrophobicity, degree of hydrolysis, ATR-FTIR spectra, and zinc binding capacity were determined. The representative samples were chosen to characterize the binding energy and surface morphology of PSPH-Zn. At last, the gastrointestinal stability of PSPH and PSPH-Zn were evaluated. Our results showed that peptides hydrolyzed by papain had the largest average molecular weight, smallest particle size, highest hydrophobicity, and the greatest zinc binding capacity. Zinc showed better gastrointestinal stability in PSPHs chelates than in its salt. Meanwhile, PSPH-Zn with higher zinc binding capacity showed better stability. The result of this study indicated pumpkin seed hydrolyzed by papain may be used as a potential source for zinc fortification. The findings in this study may provide important implications for developing plant-based zinc chelating peptides.
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http://dx.doi.org/10.3389/fnut.2021.647782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044297PMC
March 2021

Comprehensive analysis of genomic and immunological profiles in Chinese and Western hepatocellular carcinoma populations.

Aging (Albany NY) 2021 04 18;13(8):11564-11594. Epub 2021 Apr 18.

Department of Plastic and Burns Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

In this study, we explored the genomic and immune cell infiltration profiles among four distinct Hepatocellular carcinoma (HCC) types. This study included 100 patients (all tumors and adjacent liver tissues received WES sequencing) with HCC from the West China Hospital (WCH) and patients were divided into WCH-HBV-HCC group and WCH-NonHBV-HCC group. Additionally, this study included 106 HBV-related HCC (TCGA-HBV-HCC) and 69 alcoholic HCC (TCGA-Alcol-HCC) patients from the TCGA. We analyzed the high-frequency gene mutation, copy number variation (CNV), mutation spectrum, signatures and immune cell infiltration of these four groups. This study showed significant differences in gene mutation and CNV level among four HCC groups. Compared to genomic level, there is no significant difference between TCGA-HBV-HCC and TCGA-Alcol-HCC groups in fractions of tumor-infiltrating immune cells. According to the status of immune cell infiltration, patients were classified into immune-HIGH, immune-MIX and immune-LOW group, respectively. In the WCH-HBV-HCC and TCGA-HBV-HCC groups, more patients in the Immune-LOW group had TP53 mutation. Except for TP53, neither the other gene mutation nor tumor mutation burden was found to be associated with immune cell infiltration in the WCH-HBV-HCC, TCGA-HBV-HCC and TCGA-Alcol-HCC groups. In the CNV level, we found that samples with low immune infiltrate had higher number of deleted or amplified genes in the TCGA-HBV-HCC and TCGA-Alcol-HCC groups. We found comprehensive genomic heterogeneity among four HCC groups. The total gene CNV level, not the mutational burden of HCC, is associated with immune cell infiltration in HCC. TP53 mutation may injury the immune response of the HBV-related HCC.
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http://dx.doi.org/10.18632/aging.202853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109067PMC
April 2021

Comparative analysis of DNA extraction protocols for ancient soft tissue museum samples.

Zool Res 2021 May;42(3):280-286

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China.

DNA studies of endangered or extinct species often rely on ancient or degraded remains. The majority of ancient DNA (aDNA) extraction protocols focus on skeletal elements, with skin and hair samples rarely explored. Similar to that found in bones and teeth, DNA extracted from historical or ancient skin and fur samples is also extremely fragmented with low endogenous content due to natural degradation processes. Thus, the development of effective DNA extraction methods is required for these materials. Here, we compared the performance of two DNA extraction protocols (commercial and custom laboratory aDNA methods) on hair and skin samples from decades-old museum specimens to Iron Age archaeological material. We found that apart from the impact sample-specific taphonomic and handling history has on the quantity and quality of DNA preservation, skin yielded more endogenous DNA than hair of the samples and protocols tested. While both methods recovered DNA from ancient soft tissue, the laboratory method performed better overall in terms of DNA yield and quality, which was primarily due to the poorer performance of the commercial binding buffer in recovering aDNA.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175948PMC
May 2021

, another basal angiosperm species with bidirectional cytokinesis in microsporogenesis.

Plant Signal Behav 2021 Jun 15;16(6):1913308. Epub 2021 Apr 15.

Department of Plant Biology, Ecology, and Evolution, Oklahoma State University, Stillwater, Oklahoma, USA.

Comparing cellular features in microsporogenesis across taxa may yield important clues to evolution of meiosis in plants. We previously provided evidence that bidirectional cytokinesis occurs in and suggested that the same may also occur in based on a published report. Both and are basal angiosperm species that belong to the order of Magnoliales. For comparison, only unidirectional cytokinesis, either centripetal or centrifugal cytokinesis, has been found in microsporogenesis in eudicots and monocots. These observations raise the possibility that bidirectional cytokinesis is a common feature of microsporogenesis in basal angiosperms but not in eudicots and monocots. In this report, we provide evidence that bidirectional cytokinesis also occurs in another basal angiosperm species, . The new findings, together with the previous findings, indicate that bidirectional cytokinesis is a prominent feature of microsporogenesis in at least some basal angiosperm species, and it occurs independently of cytokinesis types with respect to the timing of cytokinesis and tetrad configurations.
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http://dx.doi.org/10.1080/15592324.2021.1913308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143251PMC
June 2021

Genetic variation in the Mauritian cynomolgus macaque population reflects variation in the human population.

Gene 2021 Jun 20;787:145648. Epub 2021 Apr 20.

Preclinical Safety, Research and Development, Sanofi-Aventis US, LLC, Framingham, MA, USA. Electronic address:

The cynomolgus macaque is an important species for preclinical research, however the extent of genetic variation in this population and its similarity to the human population is not well understood. Exome sequencing was conducted for 101 cynomolgus macaques to characterize genetic variation. The variant distribution frequency was 7.81 variants per kilobase across the sequenced regions, with a total of 2,770,009 single nucleotide variants identified from 2,996,041 loci. A large portion (85.6%) had minor allele frequencies greater than 5%. Enriched pathways for genes with high genetic diversity (≥10 variants per kilobase) were those involving signaling peptides and immune response. Compared to human, the variant distribution frequency and nucleotide diversity in the macaque exome was approximately 4 times greater; however the ratio of non-synonymous to synonymous variants was similar (0.735 and 0.831, respectively). Understanding genetic variability in cynomolgus macaques will enable better interpretation and human translation of phenotypic variability in this species.
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http://dx.doi.org/10.1016/j.gene.2021.145648DOI Listing
June 2021

Comparative Analysis of Gut Microbiota in Captive and Wild Oriental White Storks: Implications for Conservation Biology.

Front Microbiol 2021 25;12:649466. Epub 2021 Mar 25.

Tianjin Key Laboratory of Conservation and Utilization of Animal Diversity, College of Life Sciences, Tianjin Normal University, Tianjin, China.

The oriental white stork () is considered an endangered species based on the International Union for Conservation of Nature (IUCN) Red List. This study presents the first evidence on comparative analysis of gut microbial diversity of from various breeding conditions. To determine the species composition and community structure of the gut microbiota, 24 fecal samples from Tianjin Zoo and Tianjin Qilihai Wetland were characterized by sequencing 16S rRNA gene amplicons using the Illumina MiSeq platform. Firmicutes was found to be the predominant phylum. Analysis of community structure revealed significant differences in the species diversity and richness between the populations of the two breeding conditions. The greatest α-diversity was found in wild , while artificial breeding storks from Tianjin Zoo had the least α-diversity. Principal coordinates analysis showed that the microbial communities were different between the two studied groups. In conclusion, this study reveals the species composition and structure of the gut microbiota of oriental white storks under two breeding conditions, and our findings could contribute to the integrative conservation of this endangered bird.
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http://dx.doi.org/10.3389/fmicb.2021.649466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027120PMC
March 2021

Comparative Analysis of Gut Microbiota in Captive and Wild Oriental White Storks: Implications for Conservation Biology.

Front Microbiol 2021 25;12:649466. Epub 2021 Mar 25.

Tianjin Key Laboratory of Conservation and Utilization of Animal Diversity, College of Life Sciences, Tianjin Normal University, Tianjin, China.

The oriental white stork () is considered an endangered species based on the International Union for Conservation of Nature (IUCN) Red List. This study presents the first evidence on comparative analysis of gut microbial diversity of from various breeding conditions. To determine the species composition and community structure of the gut microbiota, 24 fecal samples from Tianjin Zoo and Tianjin Qilihai Wetland were characterized by sequencing 16S rRNA gene amplicons using the Illumina MiSeq platform. Firmicutes was found to be the predominant phylum. Analysis of community structure revealed significant differences in the species diversity and richness between the populations of the two breeding conditions. The greatest α-diversity was found in wild , while artificial breeding storks from Tianjin Zoo had the least α-diversity. Principal coordinates analysis showed that the microbial communities were different between the two studied groups. In conclusion, this study reveals the species composition and structure of the gut microbiota of oriental white storks under two breeding conditions, and our findings could contribute to the integrative conservation of this endangered bird.
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http://dx.doi.org/10.3389/fmicb.2021.649466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027120PMC
March 2021

Antifouling and Flux Enhancement of Reverse Osmosis Membrane by Grafting Poly (3-Sulfopropyl Methacrylate) Brushes.

Membranes (Basel) 2021 Mar 18;11(3). Epub 2021 Mar 18.

Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

A commercial thin film composite (TFC) polyamide (PA) reverse osmosis membrane was grafted with 3-sulfopropyl methacrylate potassium (SPMK) to produce PA-g-SPMK by atom transfer radical polymerization (ATRP). The grafting of PA was done at varied concentrations of SPMK, and its effect on the surface composition and morphology was studied by Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), optical profilometry, and contact angle analysis. The grafting of hydrophilic ionically charged PSPMK polymer brushes having acrylate and sulfonate groups resulted in enhanced hydrophilicity rendering a reduction of contact angle from 58° of pristine membrane sample labeled as MH0 to 10° for a modified membrane sample labeled as MH3. Due to the increased hydrophilicity, the flux rate rises from 57.1 L m h to 71.2 L m h, and 99% resistance against microbial adhesion ( and ) was obtained for MH3 after modification.
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http://dx.doi.org/10.3390/membranes11030213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003146PMC
March 2021