Publications by authors named "Hongbin Li"

297 Publications

Antibacterial, hemostasis, adhesive, self-healing polysaccharides-based composite hydrogel wound dressing for the prevention and treatment of postoperative adhesion.

Mater Sci Eng C Mater Biol Appl 2021 Apr 19;123:111978. Epub 2021 Feb 19.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, PR China. Electronic address:

Herein, we fabricated novel self-healing, in situ injectable, biodegradable, and non-toxic hydrogels anti-adhesion barrier materials composed of N, O-carboxymethyl chitosan (N,O-CS) and oxidized dextran (ODA) without requiring any chemical cross-linking agent or external stimuli triggers for the prevention and treatment of post-operative peritoneal adhesions. The N,O-CS/ODA hydrogels have a good suitable gelation time, good cytocompatibility and hemocompatibility, good antibacterial activity, excellent biodegradable and biocompatible, and can effectively inhibit the adhesion of fibroblasts to the wound, thereby suggesting that N,O-CS/ODA hydrogels are suitable for preventing post-operative adhesion. Meanwhile, a rat injury sidewall-cecum abrasion model is developed to investigate the efficacy of these hydrogels in achieving post-operative anti-adhesion. A significant reduction of peritoneal adhesions (10% rat with lower score adhesion) is observed in the N,O-CS/ODA-hydrogel-treated group compared with the commercial hydrogel and control groups. These results demonstrated that N,O-CS/ODA hydrogel could effectively prevent post-operative peritoneal adhesion without side effects. Therefore, the N,O-CS/ODA hydrogels with multi-functional properties exhibit great potential for the prevention and treatment of postoperative adhesion.
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http://dx.doi.org/10.1016/j.msec.2021.111978DOI Listing
April 2021

promotes cotton fiber elongation by enhancing ethylene biosynthesis.

iScience 2021 Mar 17;24(3):102199. Epub 2021 Feb 17.

College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.

Inositol-1,4,5-trisphosphate (IP) is an important second messenger and one of the products of phosphoinositide-specific phospholipase C (PIPLC)-mediated phosphatidylinositol (4,5) bisphosphate (PIP) hydrolysis. However, the function of IP in cotton is unknown. Here, we characterized the function of in cotton fiber elongation. was preferentially expressed in elongating fibers. Suppression of transcripts resulted in shorter fibers and decreased IP accumulation and ethylene biosynthesis. Exogenous application of linolenic acid (C18:3) and phosphatidylinositol (PI), the precursor of IP, improved IP and myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP) accumulation, as well as ethylene biosynthesis. Moreover, fiber length in -silenced plant was reduced after exogenous application of IP and ethylene. These results indicate that positively regulates fiber elongation and IP promotes fiber elongation by enhancing ethylene biosynthesis. Our study broadens our understanding of the function of IP in cotton fiber elongation and highlights the possibility of cultivating better cotton varieties by manipulating in the future.
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http://dx.doi.org/10.1016/j.isci.2021.102199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921840PMC
March 2021

Brain Function in Children with Obstructive Sleep Apnea: A Resting-State fMRI Study.

Sleep 2021 Mar 1. Epub 2021 Mar 1.

Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, People's Republic of China.

Objective: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and cognitive dysfunction of children with OSA.

Methods: Twenty children with OSA (7.2 ± 3.1 years, apnea hypopnea index (AHI): 16.5 ± 16.6 events/h) and 29 healthy controls (7.7 ± 2.8 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent resting-state fMRI (rs-fMRI) and T1-wighted imaging. Some children were sedated for MRI scanning. We compared amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) of children with OSA with those of healthy controls. During resting-state, the former reflects the intensity of the spontaneous neural activities, whereas the latter reflects temporal similarity of the spontaneous neural activities within a local brain region. Pearson correlation analysis was performed between these features of rs-fMRI and cognitive scores among children with OSA.

Results: Compared with controls, children with OSA showed decreased ALFF in the left angular gyrus but increased ALFF in the right insula, and decreased ReHo in the left medial superior frontal gyrus, right lingual gyrus and left precuneus. Additionally, among children with OSA, the ReHo value in the right lingual gyrus was negatively correlated with FIQ and VIQ, whereas that in the left medial superior frontal gyrus was positively correlated with VIQ.

Conclusions: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions with the former possibly being the neural mechanism of the latter.
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http://dx.doi.org/10.1093/sleep/zsab047DOI Listing
March 2021

Efficacy and safety of rescue angioplasty and/or stenting for acute large artery occlusion with underlying intracranial atherosclerosis: A systematic review and meta-analysis.

Clin Neurol Neurosurg 2021 Apr 8;203:106538. Epub 2021 Feb 8.

Department of Pediatrics, Tianjin First Central Hospital, Tianjin, 300192, China. Electronic address:

Purpose: Intracranial angioplasty and/or stenting implantation is an important rescue treatment for the management of intracranial atherosclerosis-related occlusion (ICAS-O) after mechanical thrombectomy failure, but its safety and efficacy remain unclear. We investigated the safety and efficacy of rescue intracranial angioplasty and/or stenting for emergent large artery occlusion (LAO) with underlying ICAS.

Methods: We searched for relevant full-text articles in EMBASE, PubMed and the Cochrane Central Register of Controlled Trials from inception to March 1, 2020. We calculated the odds ratios (ORs) using random-effects models for symptomatic intracranial hemorrhage (sICH), mortality, recanalization rate and favorable clinical outcome at 90 days between ICAS-O group treated by rescue therapy and Non ICAS-O group. RStudio software 1.3.959 was used to perform this meta-analysis.

Results: Ten studies were included with a total of 1639 patients, of which 450 (27.5 %) were in the ICAS-O group treated with intracranial angioplasty and/or stenting, and 1189 (72.5 %) were in the Non ICAS-O group. Overall, intracranial angioplasty and/or stenting did not improve the recanalization rate (OR, 0.67 [0.26-1.76]; p = 0.419) or favorable functional outcome (OR, 1.01 [0.64-1.58]; p = 0.97) in patients with underlying ICAS-O, and the risk of sICH (OR, 0.99 [0.59-1.68]; p = 0.983) and mortality (OR, 1.26 [0.87-1.83]; p = 0.225) did not significantly differ between ICAS-O and Non ICAS-O.

Conclusions: From these observational study results, rescue intracranial angioplasty and/or stenting seems safe in patients with emergent LAO after attempted thrombectomy, but further rigorous studies are warranted to confirm its efficacy.
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http://dx.doi.org/10.1016/j.clineuro.2021.106538DOI Listing
April 2021

Microwave ablation versus parathyroidectomy for severe secondary hyperparathyroidism in patients on hemodialysis: a retrospective multicenter study.

Int J Hyperthermia 2021 ;38(1):213-219

Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: Microwave ablation is effective for severe secondary hyperparathyroidism, but the difference in efficacy between microwave ablation and parathyroidectomy remains unclear. In this multicenter retrospective cohort study, we compared the long-term clinical efficacy of microwave ablation and parathyroidectomy for severe secondary hyperparathyroidism undergoing hemodialysis.

Materials And Methods: The patients were divided into microwave ablation and parathyroidectomy groups. The primary endpoint was the proportion of patients with intact parathyroid hormone (iPTH) concentrations within the target range (100-600 pg/mL) during the efficacy assessment phase. The secondary endpoints were (i) differences in iPTH concentrations over time between the two groups, and (ii) decreases in iPTH concentrations over time in the two groups.

Results: Microwave ablation was performed in 47/92 patients and parathyroidectomy in 45/92. Primary endpoint: iPTH concentrations within the target range were achieved during the efficacy assessment phase in 26/47 patients (55.3%) and in 14/45 (31.1%) patients in the microwave ablation and parathyroidectomy groups, respectively ( = .02). Secondary endpoints: (i) Mean iPTH concentrations during the efficacy assessment phase were significantly higher in the microwave ablation versus parathyroidectomy groups (649 ± 519 pg/mL versus 136 ± 228 pg/mL, respectively;  < .01). (ii) Mean decrease in iPTH concentration from baseline was 725 ± 605 pg/mL versus 1369 ± 478 pg/mL in the MWA versus parathyroidectomy groups, respectively ( < .01).

Conclusions: Ultrasound-guided percutaneous microwave ablation provides higher iPTH target-achieving rates than parathyroidectomy in patients with severe secondary hyperparathyroidism undergoing hemodialysis.
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http://dx.doi.org/10.1080/02656736.2021.1885754DOI Listing
January 2021

Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like.

Cancer Cell Int 2020 Jul 17;20(1):321. Epub 2020 Jul 17.

Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, China.

Background: Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human cancers. Nevertheless, the effects of lncRNAs and miRNAs on breast cancer (BC) remain to be further investigated. This study was designed to testify the roles of lncRNA antisense transcript of SATB2 protein (SATB2-AS1) and microRNA-155-3p (miR-155-3p) in BC progression.

Methods: Levels of SATB2-AS1, miR-155-3p and breast cancer metastasis suppressor 1-like (BRMS1L) in BC were determined. The prognostic role of SATB2-AS1 in BC patients was assessed. The screened cells were respectively introduced with altered SATB2-AS1 or miR-155-3p to figure out their roles in malignant phenotypes of BC cells. The effect of varied SATB2-AS1 and miR-155-3p on BC cells in vivo was observed. Dual luciferase reporter gene assay and RNA-pull down assay were implemented to detect the targeting relationship of SATB2-AS1, miR-155-3p, and BRMS1L.

Results: SATB2-AS1 and BRMS1L were decreased while miR-155-3p was increased in BC cells and tissues. Patients with lower SATB2-AS1 expression had poor prognosis. Elevated SATB2-AS1 and inhibited miR-155-3p were able to restrain malignant behaviors of BC cells in vitro, as well as decelerate tumor growth in vivo. Oppositely, inhibited SATB2-AS1 and amplified miR-155-3p had converse effects on BC cell growth. MiR-155-3p mimic abrogated the impact of overexpressed SATB2-AS1. SATB2-AS1 could sponge miR-155-3p, and BRMS1L was the target gene of miR-155-3p.

Conclusion: Elevated SATB2-AS1 and inhibited miR-155-3p could suppress the malignant phenotypes of BC cells, thereby restricting the development of BC.
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http://dx.doi.org/10.1186/s12935-020-01411-8DOI Listing
July 2020

Comparative transcriptome analysis of leaves during early stages of chilling stress in two different chilling-tolerant brown-fiber cotton cultivars.

PLoS One 2021 9;16(2):e0246801. Epub 2021 Feb 9.

China Colored-cotton (Group) Co., Ltd., Urumqi, China.

Chilling stress generates significant inhibition of normal growth and development of cotton plants and lead to severe reduction of fiber quality and yield. Currently, little is known for the molecular mechanism of brown-fiber cotton (BFC) to respond to chilling stress. Herein, RNA-sequencing (RNA-seq)-based comparative analysis of leaves under 4°C treatment in two different-tolerant BFC cultivars, chilling-sensitive (CS) XC20 and chilling-tolerant (CT) Z1612, was performed to investigate the response mechanism. A total of 72650 unigenes were identified with eight commonly used databases. Venn diagram analysis identified 1194 differentially expressed genes (DEGs) with significant up-regulation in all comparison groups. Furthermore, enrichment analyses of COG and KEGG, as well as qRT-PCR validation, indicated that 279 genes were discovered as up-regulated DEGs (UDEGs) with constant significant increased expression in CT cultivar Z1612 groups at the dimensions of both each comparison group and treatment time, locating in the enriched pathways of signal transduction, protein and carbohydrate metabolism, and cell component. Moreover, the comprehensive analyses of gene expression, physiological index and intracellular metabolite detections, and ascorbate antioxidative metabolism measurement validated the functional contributions of these identified candidate genes and pathways to chilling stress. Together, this study for the first time report the candidate key genes and metabolic pathways responding to chilling stress in BFC, and provide the effective reference for understanding the regulatory mechanism of low temperature adaptation in cotton.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872267PMC
February 2021

Comparison of the Protective Effect of Different Mild Therapeutic Hypothermia Temperatures on Intestinal Injury after Cardiopulmonary Resuscitation in Rats.

Shock 2021 Feb 3. Epub 2021 Feb 3.

Department of Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China Department of Cardiovascular Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China Department of Statistical Sciences and Operation Research, Virginia Commonwealth University, Richmond, VA, USA Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA Department of Emergency, Fujian Provincial Hospital, Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.

Background: Therapeutic temperature management (TTM) is the standard treatment protocol for unconscious post-resuscitation patients. However, there is still controversy about the ideal targeted temperature of mild hypothermia therapy. Additionally, studies about protective therapy for post-resuscitation intestinal injury are very limited. Therefore, this study was performed to explore: 1) whether mild hypothermia therapy can exert a protective effect on post-resuscitation intestinal injury; 2) the protective effect of different targeted temperatures on post-resuscitation intestinal injury and the ideal targeted temperature; 3) the potential protective mechanism of mild hypothermia therapy for post-resuscitation intestinal injury.

Methods: Ventricular fibrillation was electrically induced and untreated for 6 min while defibrillation was attempted after 8 min of cardiopulmonary resuscitation in 15 rats. After successful resuscitation, animals were randomized into three groups: (i) control; (ii) TTM-35; (iii) TTM-33. In animals of the control group, temperature was maintained at 37 ± 0.2°C for 6 hours. In animals of the two TTM groups, temperature was maintained at 33 ± 0.2°C or 35 ± 0.2°C for 6 hours, respectively. During mild hypothermia therapy, intestinal microcirculation was measured at 60, 240, and 360 min after resuscitation. Animals were euthanized 6.5 h after resuscitation. The morphological changes in the intestinal tissue, systemic and local inflammatory factors, and intestinal injury markers were measured and analyzed. The tight junction proteins in the intestinal epithelium, cell-cell contact protein E-cadherin expression, myosin light chain (MLC) and myosin light chain kinase (MLCK) levels, and the NF-κB p65 signaling pathway were analyzed by western blotting.

Results: Compared with results in the control group, mild hypothermia therapy (TTM-33 and TTM-35 groups) significantly improved post-resuscitation intestinal microcirculation and pathological scores, decreased systemic and local intestinal tissue inflammatory factor levels, inhibited the NF-κB signaling pathway and downstream MLC phosphorylation, and significantly decreased MLC phosphorylation-associated loss of intestinal tight junction proteins and E-cadherin (P < 0.05). A 33°C target temperature could exert more protective effects than 35°C on post-resuscitation intestinal injury, such as improving intestinal microcirculation, decreasing intestinal ischemia factor iFABP and plasma endotoxin levels, inhibiting the NF-κB signaling pathway and downstream MLC phosphorylation, and suppressing the loss of intestinal tight junctions and E-cadherin (P < 0.05).

Conclusions: Mild hypothermia therapy can improve post-resuscitation intestinal injury, and a targeted temperature of 33°C may confer more benefit for mitigation of intestinal injury as compared with a targeted temperature of 35°C.
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http://dx.doi.org/10.1097/SHK.0000000000001745DOI Listing
February 2021

Multiple functions of p21 in cancer radiotherapy.

J Cancer Res Clin Oncol 2021 Apr 5;147(4):987-1006. Epub 2021 Feb 5.

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, 730000, Gansu, China.

Background: Greater than half of cancer patients experience radiation therapy, for both radical and palliative objectives. It is well known that researches on radiation response mechanisms are conducive to improve the efficacy of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, transcriptionally modulated by p53 and a marker of cellular senescence. It was once considered that p21 acts as a tumour suppressor mainly to restrain cell cycle progression, thereby resulting in growth suppression. With the deepening researches on p21, p21 has been found to regulate radiation responses via participating in multiple cellular processes, including cell cycle arrest, apoptosis, DNA repair, senescence and autophagy. Hence, a comprehensive summary of the p21's functions in radiation response will provide a new perspective for radiotherapy against cancer.

Methods: We summarize the recent pertinent literature from various electronic databases, including PubMed and analyzed several datasets from Gene Expression Omnibus database. This review discusses how p21 influences the effect of cancer radiotherapy via involving in multiple signaling pathways and expounds the feasibility, barrier and risks of using p21 as a biomarker as well as a therapeutic target of radiotherapy.

Conclusion: p21's complicated and important functions in cancer radiotherapy make it a promising therapeutic target. Besides, more thorough insights of p21 are needed to make it a safe therapeutic target.
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http://dx.doi.org/10.1007/s00432-021-03529-2DOI Listing
April 2021

Genome-wide characterization of the WAK gene family and expression analysis under plant hormone treatment in cotton.

BMC Genomics 2021 Jan 28;22(1):85. Epub 2021 Jan 28.

College of Life Sciences, Shaanxi Normal University, Xi'an, 710119, China.

Background: Wall-associated kinases (WAK), one of the receptor-like kinases (RLK), function directly in the connection and communication between the plant cell wall and the cytoplasm. WAK genes are highly conserved and have been identified in plants, such as rice, but there is little research on the WAK gene family in cotton.

Results: In the present study, we identified 29 GhWAK genes in Gossypium hirsutum. Phylogenetic analysis showed that cotton WAK proteins can be divided into five clades. The results of synteny and Ka/Ks analysis showed that the GhWAK genes mainly originated from whole genome duplication (WGD) and were then mainly under purifying selection. Transcriptome data and real-time PCR showed that 97% of GhWAK genes highly expressed in cotton fibers and ovules. β-glucuronidase (GUS) staining assays showed that GhWAK5 and GhWAK16 expressed in Arabidopsis leaf trichomes. Fourteen GhWAK genes were found to possess putative gibberellin (GA) response elements in the promoter regions, 13 of which were significantly induced by GA treatment. Ten GhWAK genes contained auxin (IAA) response elements and the expression level of nine GhWAKs significantly increased under auxin treatment.

Conclusions: We provide a preliminary analysis of the WAK gene family in G. hirsutum, which sheds light on the potantial roles of GhWAK genes in cotton fiber cell development. Our data also provides a useful resource for future studies on the functional roles of GhWAK genes.
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http://dx.doi.org/10.1186/s12864-021-07378-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842020PMC
January 2021

Genome-Wide Analysis of MDHAR Gene Family in Four Cotton Species Provides Insights into Fiber Development via Regulating AsA Redox Homeostasis.

Plants (Basel) 2021 Jan 25;10(2). Epub 2021 Jan 25.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi 832003, China.

Monodehydroasorbate reductase (MDHAR) (EC1.6.5.4), a key enzyme in ascorbate-glutathione recycling, plays important roles in cell growth, plant development and physiological response to environmental stress via control of ascorbic acid (AsA)-mediated reduction/oxidation (redox) regulation. Until now, information regarding function and regulatory mechanism in have been limited. Herein, a genome-wide identification and comprehensive bioinformatic analysis of 36 family genes in four species, , , and , were performed, indicating their close evolutionary relationship. Expression analysis of in different cotton tissues and under abiotic stress and phytohormone treatment revealed diverse expression features. Fiber-specific expression analysis showed that , and were preferentially expressed in fiber fast elongating stages to reach peak values in 15-DPA fibers, with corresponding coincident observances of MDHAR enzyme activity, AsA content and ascorbic acid/dehydroascorbic acid (AsA/DHA) ratio. Meanwhile, there was a close positive correlation between the increase of AsA content and AsA/DHA ratio catalyzed by MDHAR and fiber elongation development in different fiber-length cotton cultivars, suggesting the potential important function of MDHAR for fiber growth. Following HO stimulation, demonstrated immediate responses at the levels of mRNA, enzyme, the product of AsA and corresponding AsA/DHA value, and antioxidative activity. These results for the first time provide a comprehensive systemic analysis of the gene family in plants and the four cotton species and demonstrate the contribution of MDHAR to fiber elongation development by controlling AsA-recycling-mediated cellular redox homeostasis.
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http://dx.doi.org/10.3390/plants10020227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912408PMC
January 2021

Chinese SLE Treatment and Research Group Registry (CSTAR) XIII: prevalence and risk factors for chronic scarring alopecia in patients with systemic lupus erythematosus.

Arthritis Res Ther 2021 01 11;23(1):20. Epub 2021 Jan 11.

Department of Rheumatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.

Background: Scarring alopecia in systemic lupus erythematosus (SLE) patients caused reduced life quality and prolonged disease course. This case-control study aims to survey the prevalence of scarring alopecia during the disease course of SLE and evaluate the risk factors for scarring alopecia in Chinese SLE patients.

Methods: SLE patients in Chinese SLE treatment and Research group (CSTAR) were recruited. Scarring alopecia was defined according to SLICC/ACR-DI which was collected during follow-up visits or via self-reported questionnaires. We collected demographic characteristics, common comorbidities, autoantibody profiles, disease activity status, major organ involvements, and treatment strategies of these patients at registry. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for scarring alopecia.

Results: We recruited 4792 SLE patients, and 374 (7.80%) patients had scarring alopecia. Mucocutaneous lesions (OR 2.062, p < 0.001), high SLICC/ACR-DI (OR 1.409, p < 0.001), and positive anti-Sm (OR 1.374, p = 0.029) were risk factors for scarring alopecia, while renal (OR 0.714, p = 0.028) and cardio-respiratory involvements (OR 0.347, p = 0.044), and immunosuppressant treatment (OR 0.675, p < 0.001) were significantly negative associated with it.

Conclusions: The prevalence of scarring alopecia in SLE patients is 7.80%. Active treatment strategies should be adopted to prevent scarring alopecia occurring.
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http://dx.doi.org/10.1186/s13075-020-02407-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802218PMC
January 2021

Slow Transition Path Times Reveal a Complex Folding Barrier in a Designed Protein.

Front Chem 2020 7;8:587824. Epub 2020 Dec 7.

Gene Center Munich, Ludwig-Maximilians-Universität München, Munich, Germany.

designed proteins have received wide interest as potential platforms for nano-engineering and biomedicine. While much work is being done in the design of thermodynamically stable proteins, the folding process of artificially designed proteins is not well-studied. Here we used single-molecule force spectroscopy by optical tweezers to study the folding of ROSS, a designed 2x2 Rossmann fold. We measured a barrier crossing time in the millisecond range, much slower than what has been reported for other systems. While long transition times can be explained by barrier roughness or slow diffusion, we show that isotropic roughness cannot explain the measured transition path time distribution. Instead, this study shows that the slow barrier crossing of ROSS is caused by the population of three short-lived high-energy intermediates. In addition, we identify incomplete and off-pathway folding events with different barrier crossing dynamics. Our results hint at the presence of a complex transition barrier that may be a common feature of many artificially designed proteins.
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http://dx.doi.org/10.3389/fchem.2020.587824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750197PMC
December 2020

Associations of Changes in Serum Inflammatory Factors, MMP-3, 25(OH)D and Intestinal Flora with Osteoporosis and Disease Activity in Rheumatoid Arthritis Patients.

Clin Lab 2020 Dec;66(12)

Background: To explore the associations of changes in serum inflammatory factors, matrix metalloproteinase-3 (MMP-3), 25-hydroxy vitamin D [25(OH)D], and intestinal flora with osteoporosis and disease activity in rheumatoid arthritis (RA) patients, so as to provide references for clinical diagnosis and treatment.

Methods: A total of 98 RA patients were selected as the objects of study (RA group), and divided into active-stage group (n = 56) and remission-stage group (n = 42) according to the disease activity score (DAS28). Another 50 healthy people receiving physical examination in our hospital during the same period were selected as the control group. The changes in serum inflammatory factors, MMP-3, 25(OH)D, and intestinal flora were compared among the three groups, and the osteoporosis of the subjects was analyzed in each group. Moreover, the associations of changes in serum inflammatory factors, MMP-3, 25(OH)D, and intestinal flora with osteoporosis and disease activity in RA patients were analyzed using the Pearson's method.

Results: Compared with those in the control group, the levels of serum MMP-3, interleukin-6 (IL-6), IL-10, and C-reactive protein (CRP). The Escherichia coli count were significantly increased, while the level of serum 25(OH)D, bone mineral density (BMD), and Lactobacillus and Bifidobacterium counts were significantly decreased in the active-stage group and remission-stage group, more obviously in active-stage group (p < 0.05). The osteoporosis and disease activity in RA patients were positively correlated with serum IL-6, IL-10, CRP, MMP-3, Escherichia coli and BMD, but negatively correlated with 25(OH)D, Lactobacillus and Bifidobacterium (p < 0.05), and not correlated with the sharp score (p > 0.05).

Conclusions: There are certain associations of changes in serum inflammatory factors, MMP-3, 25(OH)D, and in-testinal flora with osteoporosis and disease activity in RA patients, showing certain value in clinical application.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200242DOI Listing
December 2020

Mitochondrial Complex I Core Protein Regulates cAMP Signaling via Phosphodiesterase Pde2 and NAD Homeostasis in .

Front Microbiol 2020 26;11:559975. Epub 2020 Nov 26.

Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, United States.

The cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A (PKA) pathway of responds to nutrient availability to coordinate a series of cellular processes for its replication and survival. The elevation of cAMP for PKA signaling must be both transitory and tightly regulated. Otherwise, any abnormal cAMP/PKA pathway would disrupt metabolic potential and ergosterol synthesis and promote a stress response. One possible mechanism for controlling cAMP levels is direct induction of the phosphodiesterase gene by cAMP itself. Our earlier studies have shown that most single-gene-deletion mutants of the mitochondrial electron transport chain (ETC) complex I (CI) are hypersensitive to fluconazole. To understand the fluconazole hypersensitivity observed in these mutants, we focused upon the cAMP/PKA-mediated ergosterol synthesis in CI mutants. Two groups of the ETC mutants were used in this study. Group I includes CI mutants. Group II is composed of CIII and CIV mutants; group II mutants are known to have greater respiratory loss. All mutants are not identical in cAMP/PKA-mediated ergosterol response. We found that ergosterol levels are decreased by 47.3% in the Δ (CI core subunit mutant) and by 23.5% in Δ (CI regulator mutant). Both mutants exhibited a greater reduction of cAMP and excessive trehalose production compared with other mutants. Despite the normal cAMP level, ergosterol content decreased by 33.0% in the CIII mutant Δ as well, thereby displaying a cAMP/PKA-independent ergosterol response. While the two CI mutants have some unique cAMP/PKA-mediated ergosterol responses, we found that the degree of cAMP reduction correlates linearly with a decrease in total nicotinamide adenine dinucleotide (NAD) levels in all mutants, particularly in the seven CI mutants. A mechanism study demonstrates that overactive and cPDE activity must be the cause of the suppressive cAMP-mediated ergosterol response in the Δ and Δ. While the purpose of this study is to understand the impact of ETC proteins on pathogenesis-associated cellular events, our results reveal the importance of Ndh51p in the regulation of the cAMP/PKA pathway through Pde2p inhibition in normal physiological environments. As a direct link between Ndh51p and Pde2p remains elusive, we suggest that Ndh51p participates in NAD homeostasis that might regulate Pde2p activity for the optimal cAMP pathway state.
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http://dx.doi.org/10.3389/fmicb.2020.559975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726218PMC
November 2020

A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination.

Oncogene 2021 Feb 15;40(5):1027-1042. Epub 2020 Dec 15.

Department of General Surgery, Lanzhou University Second Hospital, 730000, Lanzhou, Gansu, China.

Dysregulation of the Wnt/β-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt pathway inhibitors being studied in preclinical or clinical settings for other cancers such as colorectal and pancreatic cancers are either too cytotoxic or insufficiently efficacious for GC. Thus, we screened new potent targets from β-catenin destruction complex associated with GC progression from clinical samples, and found that scaffolding protein RACK1 deficiency plays a significant role in GC progression, but not APC, AXIN, and GSK3β. Then, we identified its upstream regulator UBE2T which promotes GC progression via hyperactivating the Wnt/β-catenin signaling pathway through the ubiquitination and degradation of RACK1 at the lysine K172, K225, and K257 residues independent of an E3 ligase. Indeed, UBE2T protein level is negatively associated with prognosis in GC patients, suggesting that UBE2T is a promising target for GC therapy. Furthermore, we identified a novel UBE2T inhibitor, M435-1279, and suggested that M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1, resulting in suppression of GC progression with lower cytotoxicity in the meantime. Overall, we found that increased UBE2T levels promote GC progression via the ubiquitination of RACK1 and identified a novel potent inhibitor providing a balance between growth inhibition and cytotoxicity as well, which offer a new opportunity for the specific GC patients with aberrant Wnt/β-catenin signaling.
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http://dx.doi.org/10.1038/s41388-020-01572-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862066PMC
February 2021

Integrated analysis of circRNA-miRNA-mRNA network reveals potential prognostic biomarkers for radiotherapies with X-rays and carbon ions in non-small cell lung cancer.

Ann Transl Med 2020 Nov;8(21):1373

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.

Background: This work was aimed at exploring the regulatory network of non-coding RNA (ncRNA) especially circular RNA (circRNA) and microRNA (miRNA), in the sensitivity of non-small cell lung cancer (NSCLC) cells to low linear energy transfer (LET) X-ray and high-LET carbon ion irradiations.

Methods: The radioresistant NSCLC cell line A549-R11 was obtained from its parental cell line A549 through irradiation with X-rays of 2.0 Gy per fraction for 30 times. The sensitivities of A549, A549-R11 and H1299 cells exposed to X-rays and carbon ions were verified using the colony formation assay. A comprehensive circRNA-miRNA-mRNA network was constructed through the sequencing data in parental A549, acquired radioresistant A549-R11 and intrinsic radioresistant H1299 cells, and the network was further optimized according to the prognostic results from the TCGA and GEO databases.

Results: Based on high-throughput sequencing of circRNAs, we found that 40 circRNAs were up-regulated while 184 circRNAs were down-regulated in the intersection of the sets of A549-R11 and H1299 cells. Subsequently, a circRNA- miRNA-mRNA network, including 14 interactive pairs and 8 circRNAs, 4 overall survival-associated miRNAs, and 4 mRNAs, was constructed through the high-throughput data screening and bioinformatics methods.

Conclusions: Our results provide a complete understanding to the regulatory mechanism of the sensitivities to low-LET X-ray and high-LET carbon ion irradiations, and might be helpful to screen potential biomarkers for predicting the Carbon-ion radiotherapy (CIRT) and X-ray radiotherapy responses in NSCLC.
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http://dx.doi.org/10.21037/atm-20-2002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723558PMC
November 2020

Injectable, self-healing, antibacterial, and hemostatic N,O-carboxymethyl chitosan/oxidized chondroitin sulfate composite hydrogel for wound dressing.

Mater Sci Eng C Mater Biol Appl 2021 Jan 4;118:111324. Epub 2020 Aug 4.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.

Biodegradable and injectable hydrogels derived from natural polysaccharides have attracted extensive attention in biomedical applications due to their minimal invasiveness and ability to accommodate the irregular wound surfaces. In this work, we report the development of an in-situ-injectable, self-healing, antibacterial, hemostatic, and biocompatible hydrogel derived from the hybrid of N,O-carboxymethyl chitosan (N,O-CMC) and oxidized chondroitin sulfate (OCS), which did not require any chemical crosslinking. The N,O-CMC/OCS hydrogel could be readily produced under physiological conditions by varying the N,O-CMC-to-OCS ratio, relying on the Schiff base reaction between the -NH- functional groups of N,O-CMC and the -CHO functional groups of OCS. The results showed that the N,O-CMC2/OCS1 hydrogel had relatively long gelation time (133 s) and stable performances. The viability of NIH/3T3 cells and endothelial cells cultured with the N,O-CMC2/OCS1 hydrogel extract was roughly 85%, which demonstrated its low cell toxicity. Besides, the N,O-CMC2/OCS1 hydrogel revealed excellent antibacterial properties due to the inherent antibacterial ability of N,O-CMC. Importantly, the hydrogel tightly adhered to the biological tissue and demonstrated excellent in vivo hemostatic performance. Our work describing an injectable, self-healing, antibacterial, and hemostatic hydrogel derived from polysaccharides will likely hold good potential in serving as an enabling wound dressing material.
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http://dx.doi.org/10.1016/j.msec.2020.111324DOI Listing
January 2021

Early Pleistocene pollen record from the western Chinese Loess Plateau and its implications for the evolution of the East Asian Summer Monsoon.

Sci Total Environ 2021 Mar 4;761:143304. Epub 2020 Nov 4.

College of Environment and Planning, Henan University, Kaifeng 475004, China; National Demonstration Center for Environmental and Planning, Henan University, Kaifeng 475004, China.

The East Asian Summer Monsoon (EASM) is the most important and active atmospheric circulation system in Asia. However, its evolution during the Early Pleistocene, and that evolution's associated drivers, remain controversial. Here, for the first time, a high resolution pollen record was obtained from a loess-paleosol sequence located in the Lanzhou Basin, western Chinese Loess Plateau (CLP), and used to reconstruct the evolution of EASM intensity during the Early Pleistocene (2.2-1.7 Ma). The type of vegetation indicated by analysis of the pollen assemblage is comparable to the forest-steppe vegetation type currently distributed on the eastern CLP. This area's present-day mean annual temperature (MAT) and mean annual precipitation (MAP) are ~6-10 °C and ~400-550 mm, respectively, implying the existence of a stronger EASM intensity during the 2.2-1.7 Ma period. When the auxiliary function of the diversity index was applied, the Early Pleistocene EASM, as recorded by the vegetation successions identified within the loess-paleosol sequence, showed a generally stronger intensity during the 2.2-2.06 Ma period, a relatively weak intensity between 2.06 Ma and 1.97 Ma, and then a gradual intensification from 1.97 Ma until 1.7 Ma. Further comparisons demonstrated that the zonal thermal gradient in the Equatorial Pacific may have played an important role in driving the evolution of the EASM over a tectonic timescale during the Early Pleistocene. In contrast, over a sub-orbital or orbital timescale, the EASM intensity appears to have been closely correlated to global temperature variations, given that the MATs of the Early Pleistocene were higher than today's. This would imply that both low-latitude forcing and global temperature change were important drivers influencing variations in precipitation in Northern China, against a background of ongoing global warming.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143304DOI Listing
March 2021

Single molecule force spectroscopy reveals that a two-coordinate ferric site is critical for the folding of holo-rubredoxin.

Authors:
Jiayu Li Hongbin Li

Nanoscale 2020 Nov;12(44):22564-22573

Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada.

Metalloproteins play important roles in a wide range of biological processes. The folding process of metalloproteins is complex due to the synergistic effects of the folding of their polypeptide chains and the incorporation of metal cofactors. The folding mechanism of the simplest iron-sulfur protein rubredoxin, which contains one ferric ion coordinated by four cysteinyl sulfurs, is revealed using optical tweezers for the first time. The folding of the rubredoxin polypeptide chain is rapid and robust, while the reconstitution of the iron-sulfur center is greatly dependent upon the coordination state of the ferric ion on the unfolded polypeptide chain. If the ferric ion is coordinated by two neighboring cysteines, rubredoxin can readily fold with the iron-sulfur center fully reconstituted. However, if the ferric ion is only mono-coordinated, rubredoxin can fold but the iron-sulfur center is not reconstituted. Our results suggested that the folding of holo-rubredoxin follows a novel binding-folding-reconstitution mechanism, which is distinct from the folding mechanisms proposed for the folding of metalloproteins. Our study highlights the critical importance of the two-coordinate ferric site in the folding of holo-rubredoxin, which may have some important implications to our understanding of the folding mechanism of more complex metalloproteins in vivo.
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http://dx.doi.org/10.1039/d0nr06275hDOI Listing
November 2020

Loss of Endogenously Cycling Adult Cardiomyocytes Worsens Myocardial Function.

Circ Res 2021 Jan 4;128(2):155-168. Epub 2020 Nov 4.

Department of Medicine (L.A.B., A.Y., H.L., H.O.B., M.J.W.), University of Virginia, Charlottesville.

Rationale: Endogenously cycling adult cardiomyocytes increase after myocardial infarction (MI) but remain scarce and are generally thought not to contribute to myocardial function. However, this broadly held assumption has not been tested, mainly because of the lack of transgenic reporters that restrict Cre expression to adult cardiomyocytes that reenter the cell cycle.

Objective: We created and validated a new transgenic mouse, (alpha myosin heavy chain) (denoted [cardiomyocyte-specific αMHC-MerDreMer-Ki67p-RoxedCre]) that restricts Cre expression to cycling adult cardiomyocytes and uniquely integrates spatial and temporal adult cardiomyocyte cycling events based on the DNA specificities of orthologous Dre and Cre recombinases. We then created mice that expressed an inducible diphtheria toxin in adult cycling cardiomyocytes and examined the effects of ablating these endogenously cycling cardiomyocytes on myocardial function after ischemic-reperfusion (I/R) MI.

Methods And Results: A tandem transgene was designed, validated in cultured cells, and used to make transgenic mice. The transgene integrated between and and did not disrupt expression of the surrounding genes. Compared with controls, ) mice treated with Tamoxifen expressed tdTomato+ in cardiomyocytes with rare Bromodeoxyuridine+, eGFP+ cardiomyocytes, consistent with reentry of the cell cycle. We then pretreated mice with Tamoxifen to activate the reporter before sham or reperfusion (I/R) MI surgeries. Compared with Sham surgery, the I/R MI group had increased single and paired eGFP+ (enhanced green fluorescent protein)+ cardiomyocytes predominantly in the border zones (5.8±0.5 versus 3.3±0.3 cardiomyocytes per 10-micron section, N=8-9 mice per group, n=16-24 sections per mouse), indicative of cycled cardiomyocytes. The single to paired eGFP+ cardiomyocyte ratio was ≈9 to 1 (5.2±0.4 single versus 0.6±0.2 paired cardiomyocytes) in the I/R MI group after MI, suggesting that cycling cardiomyocytes were more likely to undergo polyploidy than replication. The ablation of endogenously cycling adult cardiomyocytes in (diphtheria) mice caused progressive worsening left ventricular chamber size and function after I/R MI, compared with controls.

Conclusions: Although scarce, endogenously cycling adult cardiomyocytes contribute to myocardial function after injury, suggesting that these cells may be physiologically relevant.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318277DOI Listing
January 2021

Efficacy and safety of tirofiban therapy in patients receiving endovascular treatment after large vessel ischaemic stroke: A systematic review and meta-analysis.

J Clin Neurosci 2020 Oct 18;80:112-120. Epub 2020 Aug 18.

Department of Neurology, Beichen Traditional Chinese Medical Hospital, Tianjin, China.

Background: Although tirofiban therapy is considered a potentially effective treatment to reduce the incidence of thrombotic complications in patients receiving endovascular treatment (EVT), the safety and efficacy of tirofiban remain controversial. Our objective was to investigate the efficacy and safety of EVT plus tirofiban therapy in patients with emergent large artery occlusion.

Methods: Relevant articles from randomized controlled trials (RCTs) or observational studies that compared treatment with tirofiban to treatment without tirofiban in patients undergoing EVT were retrieved from the PubMed and Embase databases. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) for the safety and efficacy outcomes based on a random effects model.

Results: Twelve studies including 2533 patients were identified for the analysis. Overall, the risk of fatal intracranial haemorrhage (ICH) was higher for the treatment with tirofiban group than for the treatment without tirofiban group in patients with large artery occlusion who underwent EVT (p = 0.002), whereas the risk of any ICH, symptomatic ICH, parenchymal haematoma type 2, in-hospital mortality and 3-month mortality did not differ significantly (p > 0.05). No significant differences in reocclusion rate, recanalization rate or excellent functional outcome were found between the patients treated with or without tirofiban, but significantly favourable functional outcome at 3 months occurred in the tirofiban group (p = 0.017).

Conclusions: Tirofiban administration in patients receiving EVT significantly improved 3-month favourable functional outcomes, whereas an increased risk of fatal ICH was also observed. Further rigorous trials are needed to verify the safety of tirofiban.
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http://dx.doi.org/10.1016/j.jocn.2020.07.040DOI Listing
October 2020

A stable organic dye catholyte for long-life aqueous flow batteries.

Chem Commun (Camb) 2020 Nov 20;56(89):13824-13827. Epub 2020 Oct 20.

State Key Laboratory for Mechanical Behavior of Materials, Shaanxi International Research Center for Soft Matter, Xi'an Jiaotong University, Xi'an 710049, China.

An organic dye, Basic blue 3 (BB3), was reported for the first time as a two-electron catholyte for aqueous redox flow batteries. The exceptional stability of BB3 enabled the full battery to achieve a high capacity retention of >99.991% per cycle during 1500 cycles.
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http://dx.doi.org/10.1039/d0cc05133kDOI Listing
November 2020

Vocal cord paralysis following lithium button battery ingestion in children.

Eur J Pediatr 2021 Apr 13;180(4):1059-1066. Epub 2020 Oct 13.

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

This study reports on vocal cord paralysis caused by esophageal button battery (BB) ingestion in children. Medical records of children with vocal cord paralysis and esophageal BB ingestion treated at a tertiary referral institute between January 2016 and March 2020 were reviewed. Five patients aged 9-58 months were identified; three were male. Each patient had accidentally swallowed a 20-mm-diameter lithium battery (3 CR2032 type and 2 CR2025 type). One battery was removed within 4 h after ingestion, and three batteries were removed within 12 h. Removal of the battery was achieved with rigid esophagoscopy in four patients and direct laryngoscopy in one patient. Four patients had bilateral, and one had unilateral vocal cord paralysis. Three patients underwent tracheotomy; two were tracheotomy-dependent until follow-up, while the third patient died of multiple organ dysfunction syndrome a month after surgery. The two cases without tracheotomy remain under close follow-up.Conclusion: Accidentally ingested button batteries should be removed promptly to avoid severe complications. Respiratory support and neurotrophic treatment in the early stage of vocal cord paralysis may be beneficial for recovery of vocal cord movement. What is Known: • Button battery ingestion in children is extremely harmful, especially when the diameter of the button battery exceeds 20 mm. • Esophageal button battery impaction can cause serious complications such as esophageal perforation, mediastinal infection, tracheoesophageal fistula, vocal cord paralysis, and life-threatening bleeding. What is New: • Vocal cord paralysis in children with button battery ingestion plays an early warning role for identifying the severity of the disease. • Early neurotrophic drugs and glucocorticoid therapy may be helpful for the recovery of vocal cord movement, thereby avoiding tracheotomy.
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http://dx.doi.org/10.1007/s00431-020-03830-1DOI Listing
April 2021

Chinese registry of rheumatoid arthritis (CREDIT): III. The transition of disease activity during follow-ups and predictors of achieving treatment target.

Int J Rheum Dis 2020 Dec 9;23(12):1719-1727. Epub 2020 Oct 9.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center on Rheumatology, Ministry of Science & Technology, Beijing, China.

Aim: The Chinese Registry of Rheumatoid Arthritis (CREDIT) is the first nationwide multi-center prospective rheumatoid arthritis (RA) registration cohort in China. This study aimed at presenting disease activities transition during follow-ups and identifying predictors to treatment response.

Method: Patients who had baseline, 3- and 6-month follow-up data from November 2016 to April 2018 were recruited. Then, we selected patients who did not reach remission (REM)/low disease activity (LDA) at baseline to investigate the predictors for treatment response.

Results: There were 979 patients included (83.00% female, mean age 51.8 and median duration 3.84 years). REM/LDA rate at baseline, 3-, and 6-month follow-up were 34.02%, 59.35% and 68.23%. Additionally, early RA has more chance to achieve targets than established RA (6 months: 59.79% vs 48.13%, P = .002). High baseline Disease Activity Score of 28 joints (DAS28) (early RA: odds ratio [OR] 1.319, P = .019; established RA: OR 1.337, P < .001), biologic disease-modifying anti-rheumatic drugs (bDMARD)/targeted synthetic DMARD combined conventional DMARD therapy (early RA: OR 9.023, P = .046) and prednisolone usage (early RA: OR 2.526, P < .001) are positively associated with Clinical Disease Assessment Index (CDAI) decreasing at 3 months. Low baseline DAS28 (REM/LDA: early RA: OR 0.650, P < .001; established RA: OR 0.612, P < .001. REM: early RA: OR 0.743, P = .021; established RA: OR 0.674, P < .001), young age (REM: early RA: OR 0.977, P = .048) and decrease of CDAI at 3 months (REM/LDA: early RA: OR 7.185, P < .001; established RA: OR 8.752, P < .001. REM: early RA: OR 5.602, P < .001; established RA: OR 4.955, P < .001) predict REM/LDA at 6 months.

Conclusion: Disease activity decreased during follow-ups. Disease duration, baseline disease activity, age, treatment strategies, and CDAI decreasing were associated with treatment response.
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http://dx.doi.org/10.1111/1756-185X.13996DOI Listing
December 2020

GhARF16-1 modulates leaf development by transcriptionally regulating the GhKNOX2-1 gene in cotton.

Plant Biotechnol J 2021 Mar 15;19(3):548-562. Epub 2020 Oct 15.

College of Life Sciences, Shaanxi Normal University, Xi'an, China.

The leaf is a crucial organ evolved with remarkable morphological diversity to maximize plant photosynthesis. The leaf shape is a key trait that affects photosynthesis, flowering rates, disease resistance and yield. Although many genes regulating leaf development have been identified in the past years, the precise regulatory architecture underlying the generation of diverse leaf shapes remains to be elucidated. We used cotton as a reference model to probe the genetic framework underlying divergent leaf forms. Comparative transcriptome analysis revealed that the GhARF16-1 and GhKNOX2-1 genes might be potential regulators of leaf shape. We functionally characterized the auxin-responsive factor ARF16-1 acting upstream of GhKNOX2-1 to determine leaf morphology in cotton. The transcription of GhARF16-1 was significantly higher in lobed-leaved cotton than in smooth-leaved cotton. Furthermore, the overexpression of GhARF16-1 led to the up-regulation of GhKNOX2-1 and resulted in more and deeper serrations in cotton leaves, similar to the leaf shape of cotton plants overexpressing GhKNOX2-1. We found that GhARF16-1 specifically bound to the promoter of GhKNOX2-1 to induce its expression. The heterologous expression of GhARF16-1 and GhKNOX2-1 in Arabidopsis led to lobed and curly leaves, and a genetic analysis revealed that GhKNOX2-1 is epistatic to GhARF16-1 in Arabidopsis, suggesting that the GhARF16-1 and GhKNOX2-1 interaction paradigm also functions to regulate leaf shape in Arabidopsis. To our knowledge, our results uncover a novel mechanism by which auxin, through the key component ARF16-1 and its downstream-activated gene KNOX2-1, determines leaf morphology in eudicots.
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http://dx.doi.org/10.1111/pbi.13484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955886PMC
March 2021

Expanding sacrificially printed microfluidic channel-embedded paper devices for construction of volumetric tissue models in vitro.

Biofabrication 2020 09 18;12(4):045027. Epub 2020 Sep 18.

Division of Engineering in Medicine, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Cambridge, MA 02139, United States of America. College of Light Industry and Textile, Qiqihar University, Qiqihar, Heilongjiang 161000, People's Republic of China. MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150001, People's Republic of China.

We report a method for expanding microchannel-embedded paper devices using a precisely controlled gas-foaming technique for the generation of volumetric tissue models in vitro. We successfully fabricated hollow, perfusable microchannel patterns contained in a densely entangled network of bacterial cellulose nanofibrils using matrix-assisted sacrificial three-dimensional printing, and demonstrated the maintenance of their structural integrity after gas-foaming-enabled expansion in an aqueous solution of NaBH. The resulting expanded microchannel-embedded paper devices showed multilayered laminar structures with controllable thicknesses as a function of both NaBH concentration and expansion time. With expansion, the thickness and porosity of the bacterial cellulose network were significantly increased. As such, cellular infiltration was promoted comparing to as-prepared, non-expanded devices. This simple technique enables the generation of truly volumetric, cost-effective human-based tissue models, such as vascularized tumor models, for potential applications in preclinical drug screening and personalized therapeutic selection.
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http://dx.doi.org/10.1088/1758-5090/abb11eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847249PMC
September 2020

Anti-aging effects of anthocyanins on neural stem cells and aging mice.

Aging (Albany NY) 2020 Sep 12;12(17):17738-17753. Epub 2020 Sep 12.

Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.

Aging is associated with neurological impairment and cognitive decline. Flavonoids are very promising in anti-aging research in mouse models. anthocyanins are rich in abundant flavonoids, but their anti-aging biological activities remain unknown. In this study, we prepared an anthocyanin extract and analyzed its effects on neural stem cell (NSC) senescence and . We isolated mouse NSCs and used cell counting kit-8 (CCK-8), cell cycle, reactive oxygen species (ROS), and immunofluorescence methods to analyze the anti-aging effects of anthocyanins as well as naringenin (Nar), which metabolic analysis revealed as an important flavonoid in anthocyanins. RNA-sequencing (RNA-seq) and enzyme-linked immuno sorbent assay (ELISA) methods were also used to investigate Nar-specific mechanisms of anti-aging. After anthocyanin treatment, NSC proliferation accelerated, and NSCs had decreased senescence markers, and reduced P16 expression. anthocyanin treatment also reversed age-dependent neuronal loss and . Nar blocked mNSC aging and improved spatial memory and cognitive abilities in aging mice through downregulation of plasma TNF-α protein. These findings suggest that anthocyanins increase NSC proliferation and improve neurogenesis with aging via Nar-induced reductions in TNF-α protein levels .
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http://dx.doi.org/10.18632/aging.103955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521483PMC
September 2020