Publications by authors named "Yi Liao"

279 Publications

miR‑383 increases the cisplatin sensitivity of lung adenocarcinoma cells through inhibition of the RBM24‑mediated NF‑κB signaling pathway.

Int J Oncol 2021 Nov 24;59(5). Epub 2021 Sep 24.

Department of Thoracic Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, P.R. China.

The expression of microRNA‑383 (miR‑383) is downregulated in a variety of tumor tissues, and it exhibits antiproliferative activity in non‑small cell lung cancer cells. In the present study, an association between the downregulation of miR‑383 expression and the deletion of chr8p22 in patients with lung adenocarcinoma was identified. The promoting effect of miR‑383 on cisplatin sensitivity was verified both and . Additionally, it was revealed that the expression of RNA binding motif protein 24 (RBM24) protein was regulated by and negatively correlated with miR‑383 expression. Ectopic expression of RBM24 or inhibition of miR‑383 decreased the chemosensitivity of parental A549 cells, whereas knockdown of RBM24 in cisplatin‑resistant A549 cells increased chemosensitivity. Mechanistically, miR‑383 interfered with the activation of nuclear factor κB (NF‑κB) signaling through repression of RBM24‑mediated phosphorylation of Rel‑like domain‑containing protein A and inhibitor α of NF‑κB. Taken together, the downregulation of miR‑383 induced RBM24 expression, which was mediated through the activation of NF‑κB signaling, to contribute to chemotherapy resistance in lung adenocarcinoma cells. The results of the present study highlight potential therapeutic targets for the clinical reversal of the chemotherapy resistance in lung adenocarcinoma.
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http://dx.doi.org/10.3892/ijo.2021.5267DOI Listing
November 2021

Performance of Xpert MTB/RIF Ultra for the Diagnosis of Pulmonary Tuberculosis Using Bronchoalveolar Lavage Samples in People Living with HIV/AIDS (PLWHA) in China: A Prospective Study.

HIV AIDS (Auckl) 2021 10;13:905-916. Epub 2021 Sep 10.

Department of Primary Health Promotion, Shenzhen Center for Disease Control and Prevention, Shenzhen City, Guangdong Province, People's Republic of China.

Background: Sputum is commonly used for the diagnostic testing of pulmonary tuberculosis (PTB), but people living with HIV/AIDS (PLWHA) usually have little sputum. Moreover, the automated molecular test, Xpert MTB/RIF assay (Xpert), has a low sensitivity in PLWHA. We aimed to estimate the performance of Xpert Ultra on the detection of Mycobacterium tuberculosis (MTB) using bronchoalveolar lavage (BAL).

Methods: From February 5, 2018 to March 30, 2019, a total of 99 PLWHA with suspected PTB at the Third People's Hospital of Shenzhen, China, were recruited. The information on demographics and medical history, blood MTB antigen-specific interferon gamma enzyme-linked immunospot assay (T-SPOT.TB), T lymphocyte subsets, and plasma HIV RNA load were collected. Computed tomography (CT) and flexible bronchoscopy were performed, and BAL and blood samples were collected. Testing of acid-fast bacilli (AFB), tuberculosis real-time fluorescence quantitative PCR (TBDNA), Ultra, Xpert, and MTB culture were conducted.

Results: Compared to BAL MTB culture for tuberculosis diagnosis, Ultra, Xpert, T-SPOT.TB, TBDNA and AFB smear had the sensitivity of 0.96 (24/25), 0.80 (20/25), 0.84 (21/25), 0.44 (11/25), and 0.12 (3/25), respectively; and the specificity of 0.92 (68/74), 0.96 (71/74), 0.93 (69/74), 0.96 (71/74), and 0.99 (73/74), respectively. Our study found that the sensitivity of Ultra was higher than that of culture and Xpert (AUC 0.92, 0.86 and 0.84, respectively). The results also indicated that PLWHA with CD4 <200 cells/mm had reduced both sensitivity (from 1.00 and 0.86 to 0.94 and 0.78, respectively) and specificity (from 0.96 and 1.00 to 0.90 and 0.41, respectively) of Ultra and Xpert for the diagnosis of PTB.

Discussion: Our data supported an increased sensitivity of Ultra compared to that of Xpert on BAL samples of PLWHA, regardless of the CD4 counts and reference diagnosis standards.
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http://dx.doi.org/10.2147/HIV.S319117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439626PMC
September 2021

CIRP promotes the progression of non-small cell lung cancer through activation of Wnt/β-catenin signaling via CTNNB1.

J Exp Clin Cancer Res 2021 Aug 31;40(1):275. Epub 2021 Aug 31.

Department of Thoracic Surgery, Southwest Hospital, Army Medical University, Chongqing, 400038, P. R. China.

Background: Cold-inducible RNA binding protein (CIRP) is a newly discovered proto-oncogene. In this study, we investigated the role of CIRP in the progression of non-small cell lung cancer (NSCLC) using patient tissue samples, cultured cell lines and animal lung cancer models.

Methods: Tissue arrays, IHC and HE staining, immunoblotting, and qRT-PCR were used to detect the indicated gene expression; plasmid and siRNA transfections as well as viral infection were used to manipulate gene expression; cell proliferation assay, cell cycle analysis, cell migration and invasion analysis, soft agar colony formation assay, tail intravenous injection and subcutaneous inoculation of animal models were performed to study the role of CIRP in NSCLC cells; Gene expression microarray was used to select the underlying pathways; and RNA immunoprecipitation assay, biotin pull-down assay, immunopurification assay, mRNA decay analyses and luciferase reporter assay were performed to elucidate the mechanisms. The log-rank (Mantel-Cox) test, independent sample T-test, nonparametric Mann-Whitney test, Spearman rank test and two-tailed independent sample T-test were used accordingly in our study.

Results: Our data showed that CIRP was highly expressed in NSCLC tissue, and its level was negatively correlated with the prognosis of NSCLC patients. By manipulating CIRP expression in A549, H460, H1299, and H1650 cell lines, we demonstrated that CIRP overexpression promoted the transition of G1/G0 phase to S phase and the formation of an enhanced malignant phenotype of NSCLC, reflected by increased proliferation, enhanced invasion/metastasis and greater tumorigenic capabilities both in vitro and in vivo. Transcriptome sequencing further demonstrated that CIRP acted on the cell cycle, DNA replication and Wnt signaling pathway to exert its pro-oncogenic action. Mechanistically, CIRP directly bound to the 3'- and 5'-UTRs of CTNNB1 mRNA, leading to enhanced stability and translation of CTNNB1 mRNA and promoting IRES-mediated protein synthesis, respectively. Eventually, the increased CTNNB1 protein levels mediated excessive activation of the Wnt/β-catenin signaling pathway and its downstream targets C-myc, COX-2, CCND1, MMP7, VEGFA and CD44.

Conclusion: Our results support CIRP as a candidate oncogene in NSCLC and a potential target for NSCLC therapy.
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http://dx.doi.org/10.1186/s13046-021-02080-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406911PMC
August 2021

Koumiss promotes Mycobacterium bovis infection by disturbing intestinal flora and inhibiting endoplasmic reticulum stress.

FASEB J 2021 09;35(9):e21777

College of Veterinary Medicine, China Agricultural University, Beijing, China.

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.
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http://dx.doi.org/10.1096/fj.202002485RRDOI Listing
September 2021

Analyzing the characteristics of immune cell infiltration in lung adenocarcinoma via bioinformatics to predict the effect of immunotherapy.

Immunogenetics 2021 10 24;73(5):369-380. Epub 2021 Jul 24.

State Key Laboratory of Biotherapy of China, Division of Pulmonary Diseases, Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Recent studies have shown that tumor immune cell infiltration (ICI) is associated with immunotherapy sensitivity and the prognosis of lung adenocarcinoma (LUAD). However, the immunoinfiltrative landscape of LUAD has not been elucidated. We propose two computational algorithms to unravel the ICI landscape to evaluate the efficacy of immunotherapy in LUAD patients. The raw data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed. After merging these datasets and removing the batch differences, we used the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm to obtain the immune cell content of all the samples. The unsupervised consistency clustering algorithm was used to analyze the ICI subtypes, and three subgroups were obtained. In addition, the unsupervised consistency clustering algorithm was used to analyze the differentially expressed genes (DEGs) of the ICI subtypes and obtain three ICI gene clusters. Finally, the ICI score was determined by using principal component analysis (PCA) for the gene signature. The ICI score of LUAD patients ranged from - 32.26 to 12.89 and represents the prognosis and the response to immunotherapy. High ICI scores were characterized by the T cell receptor signaling pathway, B cell receptor signaling pathway, and natural killer cell-mediated cytotoxicity, suggesting that some immune cells were activated and had increased activity, which may be the cause of the better prognosis for patients with high ICI scores. Additionally, patients with higher ICI scores showed a significant immune therapeutic advantage and clinical benefit. This study shows that the ICI score may be a potent prognostic biomarker and predictor of therapy with immune checkpoint inhibitors.
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http://dx.doi.org/10.1007/s00251-021-01223-8DOI Listing
October 2021

A minor review of microRNA-338 exploring the insights of its function in tumorigenesis.

Biomed Pharmacother 2021 Jul 14;139:111720. Epub 2021 May 14.

Shenzhen Key Laboratory of Tissue Engineering, Department of Orthopedics, Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University), Shenzhen 518035, Guangdong, China. Electronic address:

MicroRNAs(miRNAs) are small non-coding RNAs which have a critical role in various biological processes via direct binding and post-transcriptionally regulating targeted genes expression. More than one-half of human genes were regulated by miRNAs and their aberrant expression was detected in various human diseases, including cancers. miRNA-338 is a new identified miRNA and increasing evidence show that miRNA-338 participates in the progression of lots of cancers, such as lung cancer, hepatocellular cancer, breast cancer, glioma, and so on. Although a range of targets and signaling pathways such as MACC1 and Wnt/β-catenin signaling pathway were illustrated to be regulated by miRNA-338, which functions in tumor progression are still ambiguous and the underlying molecular mechanisms are also unclear. Herein, we reviewed the latest studies in miRNA-338 and summarized its roles in different type of human tumors, which might provide us new idea for further investigations and potential targeted therapy.
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http://dx.doi.org/10.1016/j.biopha.2021.111720DOI Listing
July 2021

The Use of Nice Knots Cerclage to Aid Reduction and Fixation of Metacarpal Fractures.

Plast Reconstr Surg 2021 Aug;148(2):338e-339e

Department of Orthopaedic Surgery, Karamay Central Hospital, Karamay, People's Republic of China.

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http://dx.doi.org/10.1097/PRS.0000000000008182DOI Listing
August 2021

Distinct changes of brain cortical thickness relate to post-treatment outcomes in children with epilepsy.

Seizure 2021 Oct 13;91:181-188. Epub 2021 Jun 13.

Department of Radiology, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, National Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Purpose: In the current study, we examined the potential of neuroanatomic measures to cluster patients into different subgroups and established their clinical relevance to post-treatment outcomes.

Methods: We included seventy-two children with epilepsy (aged 14-195 months) who were treated with anti-seizure medication alone and 39 healthy participants (aged 36-60 months). High-resolution T1-weighted imaging was performed for all participants, and brain cortical thickness measurements were obtained for 68 cortical regions for each of them. Amongst the patients, data-driven hierarchical cluster analysis was performed using the selected cortical thickness measures as features. The average thickness measures in each of the 68 brain regions were then compared between patient subgroups and healthy controls.

Results: Two distinct patient subgroups were identified but were not related to the clinical types. Patients within subgroup 1 (n = 56) had a significantly higher rate of recurrent seizure than those in subgroup 2 (n = 16) (41.1% vs. 14.3%, p<0.05), while the follow-up time or medication did not differ between them. This finding was further confirmed by a recent follow-up through phone calls. The demographic variables, rate of electroencephalogram abnormalities, or sleep problems did not significantly differ between patient subgroups. Compared with healthy controls, patients in subgroup 1 showed significantly increased cortical thickness in the neocortex, whereas patients in subgroup 2 only showed regional cortical thinning in the right superior temporal gyrus.

Conclusion: These findings suggest the potential existence of distinct subgroups of children with epilepsy that were especially relevant to the differential patterns of post-treatment outcomes, with regional cortical thinning in the temporal regions relative to controls predicting lower risk of recurrent seizure.
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http://dx.doi.org/10.1016/j.seizure.2021.06.010DOI Listing
October 2021

Antegrade intramedullary fixation for adolescent fifth metacarpal neck fracture and its impact on epiphyseal growth.

BMC Musculoskelet Disord 2021 Jun 15;22(1):546. Epub 2021 Jun 15.

Department of Surgical Center, Karamay Central Hospital of Xinjiang, 834000, Karamay, China.

Background: Antegrade intramedullary nailing (AIMN) with Kirschner wire (K-wire) is a minimally invasive osteosynthesis technique. This procedure has been widely performed to treat the fifth metacarpal neck fracture (FMNF) in adults. This study was performed to determine whether using AIMN with a single K-wire to treat FMNF in adolescents would have good clinical and radiographic outcomes.

Methods: In this retrospective study, 21 children (aged 11-16 years) with FMNF were treated using AIMN with a single K-wire from May 2017 to January 2020 in our hospital. Indications for intervention were severe displacement with malrotation deformity, apex dorsal angulation of greater than 40°, or both. Collected data included apex dorsal angulation, range of motion (ROM) in the fifth metacarpophalangeal (MCP) joint, Visual Analog Scale (VAS) for pain, grip strength, and Disabilities of the Arm, Shoulder, and Hand (DASH) score.

Results: All patients were followed up for 12-24 months (average, 16.57 months), and all patients obtained anatomical reduction postoperatively. The healing time was 2.69 ± 0.83 months (range, 2-4 months). Average apex dorsal angulation was reduced significantly from 44.49°±2.64° to 15.74°±2.47° (P < 0.001). The average ROM in the MCP joint and apex dorsal angulation of the injured side were not significantly different from those of the uninjured side. The average DASH score was 1.76 ± 1.48 (range, 0-4), the mean VAS was 0.19 ± 0.60 (range, 0-2), and the mean grip strength was 91.55 %±4.52 % (range, 85-101 %). No secondary displacement, dysfunction, nonunion, infection, or osteonecrosis was observed during the follow-up. Although premature epiphyseal closure was found in one patient, no long-term clinical finding of angulation or shortening was identified.

Conclusions: Antegrade intramedullary fixation with single K-wire was an effective and reliable technique that successfully resulted in good functional and cosmetic outcomes for treating adolescents with FMNF. The impact on the growth plate was low in this population given that most patients were at or approaching skeletal maturity.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1186/s12891-021-04436-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204464PMC
June 2021

Regulation of Thermally Activated Delayed Fluorescence to Room-Temperature Phosphorescent Emission Channels by Controlling the Excited-States Dynamics via J- and H-Aggregation.

Angew Chem Int Ed Engl 2021 Aug 7;60(33):18059-18064. Epub 2021 Jul 7.

Institute of Molecule Plus, Scholl of Chemical Engineering and Technology, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, China.

Control of excited-state dynamics is key in tuning room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) emissions but is challenging for organic luminescent materials (OLMs). We show the regulation of TADF and RTP emissions of a boron difluoride β-acetylnaphthalene chelate (βCBF ) by controlling the excited-state dynamics via its J- and H-aggregation states. Two crystalline polymorphs emitting green and red light have been controllably obtained. Although both monoclinic, the green and red crystals are dominated by J- and H-aggregation, respectively, owing to different molecular packing arrangements. J-aggregation significantly reduces the energy gap between the lowest singlet and triplet excited states for ultra-fast reverse intersystem crossing (RISC) and enhances the radiative singlet decay, together leading to TADF. The H-aggregation accelerates the ISC and suppresses the radiative singlet decay, helping to stabilize the triplet exciton for RTP.
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http://dx.doi.org/10.1002/anie.202103192DOI Listing
August 2021

Pan-genome analysis of 33 genetically diverse rice accessions reveals hidden genomic variations.

Cell 2021 Jun 28;184(13):3542-3558.e16. Epub 2021 May 28.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University, Chengdu, Sichuan, China. Electronic address:

Structural variations (SVs) and gene copy number variations (gCNVs) have contributed to crop evolution, domestication, and improvement. Here, we assembled 31 high-quality genomes of genetically diverse rice accessions. Coupling with two existing assemblies, we developed pan-genome-scale genomic resources including a graph-based genome, providing access to rice genomic variations. Specifically, we discovered 171,072 SVs and 25,549 gCNVs and used an Oryza glaberrima assembly to infer the derived states of SVs in the Oryza sativa population. Our analyses of SV formation mechanisms, impacts on gene expression, and distributions among subpopulations illustrate the utility of these resources for understanding how SVs and gCNVs shaped rice environmental adaptation and domestication. Our graph-based genome enabled genome-wide association study (GWAS)-based identification of phenotype-associated genetic variations undetectable when using only SNPs and a single reference assembly. Our work provides rich population-scale resources paired with easy-to-access tools to facilitate rice breeding as well as plant functional genomics and evolutionary biology research.
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http://dx.doi.org/10.1016/j.cell.2021.04.046DOI Listing
June 2021

Brain metabolic characteristics distinguishing typical and atypical benign epilepsy with centro-temporal spikes.

Eur Radiol 2021 May 29. Epub 2021 May 29.

Department of Nuclear Medicine and Medical PET Center, The Second Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Zhejiang, 310009, Hangzhou, China.

Objectives: Atypical benign epilepsy with centro-temporal spikes (BECTS) have less favorable outcomes than typical BECTS, and thus should be accurately identified for adequate treatment. We aimed to investigate the glucose metabolic differences between typical and atypical BECTS using F-fluorodeoxyglucose positron emission tomography ([F]FDG PET) imaging, and explore whether these differences can help distinguish.

Methods: Forty-six patients with typical BECTS, 31 patients with atypical BECTS and 23 controls who underwent [F]FDG PET examination were retrospectively involved. Absolute asymmetry index (|AI|) was applied to evaluate the severity of metabolic abnormality. Glucose metabolic differences were investigated among typical BECTS, atypical BECTS, and controls by using statistical parametric mapping (SPM). Logistic regression analyses were performed based on clinical, PET, and hybrid features.

Results: The |AI| was found significantly higher in atypical BECTS than in typical BECTS (p = 0.040). Atypical BECTS showed more hypo-metabolism regions than typical BECTS, mainly located in the fronto-temporo-parietal cortex. The PET model had significantly higher area under the curve (AUC) than the clinical model (0.91 vs. 0.70, p = 0.006). The hybrid model had the highest sensitivity (0.90), specificity (0.85), and accuracy (0.87) of all three models.

Conclusions: Atypical BECTS showed more widespread and severe hypo-metabolism than typical BECTS, depending on which the two groups can be well distinguished. The combination of metabolic characteristics and clinical variables has the potential to be used clinically to distinguish between typical and atypical BECTS.

Key Points: • Distinguishing between typical and atypical BECTS is very important for the formulation of treatment regimens in clinical practice. • Atypical BECTS showed more widespread and severe hypo-metabolism than typical BECTS, mainly located in the fronto-temporo-parietal cortex. • The logistic regression model based on PET outperformed that based on clinical characteristics in classification of typical and atypical BECTS, and the hybrid model achieved the best classification performance.
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http://dx.doi.org/10.1007/s00330-021-08051-0DOI Listing
May 2021

Caspase-1 inhibits IFN-β production via cleavage of cGAS during M. bovis infection.

Vet Microbiol 2021 Jul 15;258:109126. Epub 2021 May 15.

Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100093, China. Electronic address:

Mycobacterium bovis (M. bovis) infection triggers cytokine production via pattern recognition receptors. These cytokines include type I interferons (IFNs) and interleukin-1β (IL-1β). Excessive type I IFN levels impair host resistance to M. bovis infection. Therefore, strict control of type I IFN production is helpful to reduce pathological damage and bacterial burden. Here, we found that a deficiency in caspase-1, which is the critical component of the inflammasome responsible for IL-1β production, resulted in increased IFN-β production upon M. bovis infection. Subsequent experiments demonstrated that caspase-1 activation reduced cyclic GMP-AMP synthase (cGAS) expression, thereby inhibiting downstream TANK-binding kinase 1 (TBK1)- interferon regulatory factor 3 (IRF3) signaling and ultimately reducing IFN production. A deficiency in caspase-1 activation enhanced the bacterial burden during M. bovis infection in vitro and in vivo and aggravated pathological lesion formation. Thus, caspase-1 activation reduced IFN-β production upon M. bovis infection by dampening cGAS-TBK1-IRF3 signaling, suggesting that the inflammasome protects hosts by negatively regulating harmful cytokines.
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http://dx.doi.org/10.1016/j.vetmic.2021.109126DOI Listing
July 2021

Conservative management of avascular necrosis of the metacarpal head: A case report and brief review.

Medicine (Baltimore) 2021 05;100(20):e26083

Department of Orthopaedic Surgery, Xiangya Hospital, Central South University, Changsha.

Rationale: Avascular necrosis (AVN) of the metacarpal head is rare, and there is no clear consensus on treatment. The main aim of this study was to discuss the possible pathologic-mechanics of its development, epidemiology, radiographic features, and outcome after conservative treatment.

Patient Concerns: A 14-year-old male with a history of fractures in little finger complained of right-hand pain with a limited range of motion for 1 month. Diagnosis: Imaging examination confirmed the diagnosis of AVN in the long metacarpal finger and ring finger.

Interventions: The patient was treated using non-surgical management, such as splint immobilization, non-steroidal anti-inflammatory drugs, and physiotherapy.

Outcomes: At the last follow-up 26 months later, the patient was in complete remission with no residual symptoms. Magnetic resonance imaging (MRI) confirmed excellent remodeling and regeneration in the metacarpal head.

Lessons: Metacarpal head necrosis typically occurs in adolescent patients with a history of trauma. Conservative treatment may sometimes have an excellent prognosis.
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http://dx.doi.org/10.1097/MD.0000000000026083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136993PMC
May 2021

NGFR Increases the Chemosensitivity of Colorectal Cancer Cells by Enhancing the Apoptotic and Autophagic Effects of 5-fluorouracil the Activation of S100A9.

Front Oncol 2021 30;11:652081. Epub 2021 Apr 30.

Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Colorectal cancer (CRC) is currently the third leading cause of cancer-related deaths worldwide, and 5-fluorouracil (5-FU)-based chemotherapies serve as important adjuvant therapies before and after surgery for CRC. However, the efficacy of CRC chemotherapy is limited by chemoresistance, and therefore the discovery of novel markers to indicate chemosensitivity is essential. Nerve growth factor receptor (NGFR), a cell surface receptor, is involved in cell death and survival. Our previous study indicated that NGFR acts as a tumor suppressor, and high expression is associated with better outcomes in patients receiving 5-FU-based adjuvant chemotherapy after surgery. The aim of this study was to investigate the effect of NGFR on the chemotherapeutic response in CRC. Chemosensitivity was investigated using DLD1 and HCT8 cells after NGFR transfection. Apoptosis was investigated by flow cytometry. Autophagy was assessed using GFP-LC3B transient transfection. Gene expression was measured using an mRNA microarray. Beclin-1 and Bcl-2 protein expressions were assessed by western blot. NGFR and S100 calcium-binding protein A9 (S100A9) expressions in CRC patients were investigated by immunohistochemistry. The results showed that the half maximal inhibitory concentration of NGFR-transfected cells was lower than that of controls in DLD1 and HCT8 cells after 5-FU treatment, and cell viability was lower than in empty-vector cells. Tumor sizes were also smaller than in empty-vector cells . The percentages of apoptotic and autophagic cells were higher in NGFR-transfected cells. NGFR elevated the expression of S100A9 after 5-FU treatment. The combination of Bcl-2 and Beclin-1 was significantly suppressed by overexpressed NGFR. Five-year overall and disease-free survival in NGFR+/S100A9+ patients was better than in NGFR-/S100A9- patients. This study's findings suggest that NGFR may serve as a marker predicting CRC patients' chemosensitivity.
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http://dx.doi.org/10.3389/fonc.2021.652081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120287PMC
April 2021

[Analysis and prenatal diagnosis of FMR1 gene mutations among patients with unexplained mental retardation].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 May;38(5):439-445

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.

Objective: To analyze the (CGG)n repeats of FMR1 gene among patients with unexplained mental retardation.

Methods: For 201 patients with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by PCR and FragilEase PCR. Prenatal diagnosis was provided to carriers of pre- and full-mutations. The pattern of X chromosome inactivation (XCI) was determined for women with mental retardation and full mutations.

Results: For the 201 patients with unexplained mental retardation, 15 were identified with full mutations of the FMR1 gene. The prevalence of fragile X syndrome (FXS) in patients with unexplained mental retardation was determined as 7.5% (15/201). Prenatal diagnosis was provided for 6 pregnant women with pre- or full mutations. Analysis revealed that women with mental retardation and full FMR1 mutations exhibited a skewed XCI pattern with primary expression of the X chromosome carrying the mutant allele.

Conclusion: FXS has a high incidence among patients with unexplained mental retardation. Analysis of FMR1 gene (CGG)n repeats in patients with unexplained mental retardation can facilitate genetic counseling and prenatal diagnosis for their families. FMR1 gene (CGG)n repeats screening should be recommended for patients with unexplained mental retardation.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200513-00344DOI Listing
May 2021

The circadian clock ensures successful DNA replication in cyanobacteria.

Proc Natl Acad Sci U S A 2021 May;118(20)

Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637;

Disruption of circadian rhythms causes decreased health and fitness, and evidence from multiple organisms links clock disruption to dysregulation of the cell cycle. However, the function of circadian regulation for the essential process of DNA replication remains elusive. Here, we demonstrate that in the cyanobacterium , a model organism with the simplest known circadian oscillator, the clock generates rhythms in DNA replication to minimize the number of open replication forks near dusk that would have to complete after sunset. Metabolic rhythms generated by the clock ensure that resources are available early at night to support any remaining replication forks. Combining mathematical modeling and experiments, we show that metabolic defects caused by clock-environment misalignment result in premature replisome disassembly and replicative abortion in the dark, leaving cells with incomplete chromosomes that persist through the night. Our study thus demonstrates that a major function of this ancient clock in cyanobacteria is to ensure successful completion of genome replication in a cycling environment.
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http://dx.doi.org/10.1073/pnas.2022516118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157973PMC
May 2021

MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3.

Oncol Rep 2021 Jul 6;46(1). Epub 2021 May 6.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, P.R. China.

MDM2 proto‑oncogene, E3 ubiquitin protein ligase (MDM2) is a well‑known oncogene and has been reported to be closely associated with epithelial‑to‑mesenchymal transition (EMT). The present study first demonstrated that the expression levels of MDM2 were markedly increased in TGF‑β‑induced EMT using quantitative PCR and western blotting. In addition, MDM2 was demonstrated to be associated with pathological grade in clinical glioma samples by immunohistochemical staining. Furthermore, overexpression of MDM2 promoted EMT in glioma, lung cancer and breast cancer cell lines using a scratch wound migration assay. Subsequently, the present study explored the mechanism by which MDM2 promoted EMT and revealed that MDM2 induced EMT by upregulating EMT‑related transcription factors via activation of the B‑Raf signaling pathway through tyrosine 3‑monooxygenase activation protein ε using RNA sequencing and western blotting. This mechanism depended on the p53 gene. Furthermore, experiments and the colony formation experiment demonstrated that MDM2 could promote tumor progression and induce EMT via the B‑Raf signaling pathway. Since EMT contributes to increased drug resistance in tumor cells, the present study also explored the relationship between MDM2 and drug sensitivity using an MTT assay, and identified that MDM2 promoted cell insensitivity to silibinin treatment in an EMT‑dependent manner. This finding is crucial for the development of cancer therapies and can also provide novel research avenues for future biological and clinical studies.
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http://dx.doi.org/10.3892/or.2021.8071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129971PMC
July 2021

Environmental specialization and cryptic genetic divergence in two massive coral species from the Florida Keys Reef Tract.

Mol Ecol 2021 07 10;30(14):3468-3484. Epub 2021 Jun 10.

Department of Integrative Biology, University of Texas at Austin, Austin, TX, USA.

Broadcast-spawning coral species have wide geographical ranges spanning strong environmental gradients, but it is unclear how much spatially varying selection these gradients actually impose. Strong divergent selection might present a considerable barrier for demographic exchange between disparate reef habitats. We investigated whether the cross-shelf gradient is associated with spatially varying selection in two common coral species, Montastraea cavernosa and Siderastrea siderea, in the Florida Keys. To this end, we generated a de novo genome assembly for M. cavernosa and used 2bRAD to genotype 20 juveniles and 20 adults of both species from each of the three reef zones to identify signatures of selection occurring within a single generation. Unexpectedly, each species was found to be composed of four genetically distinct lineages, with gene flow between them still ongoing but highly reduced in 13.0%-54.7% of the genome. Each species includes two sympatric lineages that are only found in the deep (20 m) habitat, while the other lineages are found almost exclusively on the shallower reefs (3-10 m). The two "shallow" lineages of M. cavernosa are also specialized for either nearshore or offshore: comparison between adult and juvenile cohorts indicates that cross-shelf migrants are more than twice as likely to die before reaching adulthood than local recruits. S. siderea and M. cavernosa are among the most ecologically successful species on the Florida Keys Reef Tract, and this work offers important insight into the genomic background of divergent selection and environmental specialization that may in part explain their resilience and broad environmental range.
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http://dx.doi.org/10.1111/mec.15931DOI Listing
July 2021

Apoptotic caspases suppress Mycobacterium bovis-induced IFN-β production in murine macrophage.

J Infect 2021 07 20;83(1):61-68. Epub 2021 Apr 20.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

Caspases are classified as inflammatory or apoptotic category. Inflammatory caspases participate in inflammasome activation, while apoptotic caspases mediate apoptotic activation. Previous studies have shown that apoptotic caspases prevent the production of IFN-β during apoptosis or virus infection. However, the relationship between apoptotic caspases and IFN-β production during intracellular bacterial infection is still unclear. Here, we investigated the role of apoptotic caspases in IFN-β production induced by Mycobacterium bovis (M. bovis) infection. M. bovis is an intracellular bacterium and belongs to the Mycobacterium tuberculosis complex. M. bovis infection can cause tuberculosis in animals and human beings. In the current study, we found that M. bovis infection triggered mitochondrial stress, which caused the leakage of cytochrome c into the cytoplasm, and in turn, activated the downstream caspase-9 and-3. Furthermore, our results showed that activation of apoptotic caspases reduced IFN-β production during M. bovis infection and vice versa. Confocal microscopy analysis revealed that apoptotic caspases prevented IFN-β production by decreasing p-IRF3 nuclear translocation. Our findings demonstrate that apoptotic caspases negatively regulate the production of IFN-β induced by an intracellular bacterial infection.
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http://dx.doi.org/10.1016/j.jinf.2021.04.014DOI Listing
July 2021

Experimental and Theoretical Characterization of Ultrafast Water-Soluble Photochromic Photoacids.

J Phys Chem B 2021 04 19;125(16):4120-4131. Epub 2021 Apr 19.

Department of Chemistry, University of Michigan, 930 North University Avenue Ann Arbor, Michigan 48109-1055, United States.

UV-visible transient absorption spectroscopy and quantum mechanical simulations are combined to elucidate the photochemical mechanism of two metastable merocyanine/spiropyran photoacids, 2-[()-2-(2-hydroxyphenyl)ethenyl]-3,3-dimethyl-1-(3-sulfopropyl)-3-indol-1-ium (phenylhydroxy-MCH) and 2-[()-2-(1-indazol-7-yl)ethenyl]-3-(3-sulfopropyl)-1,3-benzothiazol-3-ium (indazole-MCH). Transient absorption spectra demonstrate that -acid isomerization to the form results in deprotonation on a picosecond time scale. Ring closure to form spiropyran follows promptly from the appropriate conformation or follows at longer time delays (≫3.5 ns) following a barrier crossing for single-bond isomerization to the appropriate conformation. Consistent with the results of Berton et al. [ 2020, 11, 8457-8468] , we find that -phenylhydroxy-MCH is a stronger acid than -phenylhydroxy-MCH. The decrease in p upon isomerization is further investigated to benchmark quantum chemical methods for their accuracy. Calculations were performed with nine levels of theory including continuum solvent models and explicit water. The calculations are not sufficient to describe the Δp following isomerization of these photoacids, and more work is necessary to properly evaluate the physical basis for the acidity of the photoacids.
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http://dx.doi.org/10.1021/acs.jpcb.1c00644DOI Listing
April 2021

[Analysis of FMR1 gene CGG repeats among patients with diminished ovarian reserve].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):343-346

Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.

Objective: To explore the correlation between Fragile X mental retardation gene-1 (FMR1) gene CGG repeats with diminished ovarian reserve (DOR).

Methods: For 214 females diagnosed with DOR, DNA was extracted from peripheral blood samples. FMR1 gene CGG repeats were determined by PCR and capillary electrophoresis.

Results: Three DOR patients were found to carry FMR1 premutations, and one patient was found to carry gray zone FMR1 repeats. After genetic counseling, one patient and the sister of another patient, both carrying FMR1 permutations, conceived naturally. Prenatal diagnosis showed that both fetuses have carried FMR1 permutations.

Conclusion: FMR1 gene permutation may be associated with DOR. Determination of FMR1 gene CGG repeats in DOR patients can provide a basis for genetic counseling and guidance for reproduction.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200304-00129DOI Listing
April 2021

Prognostic and clinicopathological value of BUB1B expression in patients with lung adenocarcinoma: a meta-analysis.

Expert Rev Anticancer Ther 2021 Jul 7;21(7):795-803. Epub 2021 Apr 7.

Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: Abnormal BUB1B expression has been proven to be related to the poor prognosis of various tumors. This meta-analysis aimed to identify the prognostic role of BUB1B in patients with lung adenocarcinoma (LUAD).

Research Design And Methods: Relevant studies from the PubMed, Embase, Web of Science, and Cochrane Library databases and two public databases that stored sequencing data were retrieved. The standardized mean difference (SMD) and 95% confidence intervals (CIs) for the association between the BUB1B expression level and clinical characteristics were calculated. Pooled hazard ratios (HRs) and 95% CIs were calculated to estimate the association between BUB1B expression and survival outcomes.

Results: A total of 16 studies involving 2771 LUAD patients with BUB1B expression were included in this meta-analysis. Patients with older age showed low BUB1B expression. High BUB1B expression was associated with male sex, a smoking history, and an advanced TNM stage. High BUB1B expression was predictive of poor overall survival (OS) and progression-free survival (PFS). In addition, no publication bias was found.

Conclusions: This meta-analysis demonstrates that BUB1B is a significant biomarker for a poor prognosis and poor clinicopathological outcomes in patients with LUAD.
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http://dx.doi.org/10.1080/14737140.2021.1908132DOI Listing
July 2021

Anisotropic shock responses of nanoporous Al by molecular dynamics simulations.

PLoS One 2021 17;16(3):e0247172. Epub 2021 Mar 17.

Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing, China.

Mechanical responses of nanoporous aluminum samples under shock in different crystallographic orientations (<100>, <111>, <110>, <112> and <130>) are investigated by molecular dynamics simulations. The shape evolution of void during collapse is found to have no relationship with the shock orientation. Void collapse rate and dislocation activities at the void surface are found to strongly dependent on the shock orientation. For a relatively weaker shock, void collapses fastest when shocked along the <100> orientation; while for a relatively stronger shock, void collapses fastest in the <110> orientation. The dislocation nucleation position is strongly depended on the impacting crystallographic orientation. A theory based on resolved shear stress is used to explain which slip planes the earliest-appearing dislocations prefer to nucleate on under different shock orientations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247172PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968703PMC
August 2021

A donor-π-acceptor aggregation-induced emission compound serving as a portable fluorescent sensor for detection and differentiation of methanol and ethanol in the gas phase.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 1;252:119515. Epub 2021 Feb 1.

Department of Chemistry, Capital Normal University, Beijing 100048, China. Electronic address:

The design strategy of aggregation-induced emission (AIE) fluorophores with donor-π-acceptor (D-π-A) conjugation structure has greatly contributed to the development of luminescent materials and devices, including volatile organic compounds (VOCs) sensors. In this work, a D-π-A fluorophore DEBAB was synthesized, showing both AIE and intramolecular charge transfer (ICT) properties as confirmed by spectroscopic data and quantum chemical calculations. Furthermore, there is notable emission-enhancement when DEBAB is exposed to small-molecule alcohols, such as methanol and ethanol. Based on this phenomenon, a portable film sensor was fabricated, capable of detecting methanol and ethanol in gas phase, with detection limit (DL) as low as 8.02 ppm. Our systematic investigation suggests that hydrogen-bonding may be formed between DEBAB and alcohols, intensifying the AIE efficacy while influencing the ICT process. This working mechanism is supported by density functional theory (DFT) calculations including electrostatic potential mapping and molecular total energy. In addition, a sensor array was fabricated on a cellulose paper strip, showing different levels of emission changing in response to alcohols. Thus the detection and differentiation of methanol and ethanol are enabled.
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http://dx.doi.org/10.1016/j.saa.2021.119515DOI Listing
May 2021

Topologically associating domains and their role in the evolution of genome structure and function in .

Genome Res 2021 03 9;31(3):397-410. Epub 2021 Feb 9.

Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697, USA.

Topologically associating domains (TADs) were recently identified as fundamental units of three-dimensional eukaryotic genomic organization, although our knowledge of the influence of TADs on genome evolution remains preliminary. To study the molecular evolution of TADs in species, we constructed a new reference-grade genome assembly and accompanying high-resolution TAD map for Comparison of and , which are separated by ∼49 million years of divergence, showed that ∼30%-40% of their genomes retain conserved TADs. Comparative genomic analysis of 17 species revealed that chromosomal rearrangement breakpoints are enriched at TAD boundaries but depleted within TADs. Additionally, genes within conserved TADs show lower expression divergence than those located in nonconserved TADs. Furthermore, we found that a substantial proportion of long genes (>50 kbp) in (42%) and (26%) constitute their own TADs, implying transcript structure may be one of the deterministic factors for TAD formation. By using structural variants (SVs) identified from 14 strains, its three closest sibling species from the species complex, and two obscura clade species, we uncovered evidence of selection acting on SVs at TAD boundaries, but with the nature of selection differing between SV types. Deletions are depleted at TAD boundaries in both divergent and polymorphic SVs, suggesting purifying selection, whereas divergent tandem duplications are enriched at TAD boundaries relative to polymorphism, suggesting they are adaptive. Our findings highlight how important TADs are in shaping the acquisition and retention of structural mutations that fundamentally alter genome organization.
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http://dx.doi.org/10.1101/gr.266130.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919452PMC
March 2021

Evolution of genome structure in the species complex.

Genome Res 2021 03 9;31(3):380-396. Epub 2021 Feb 9.

Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California 92697, USA.

The rapid evolution of repetitive DNA sequences, including satellite DNA, tandem duplications, and transposable elements, underlies phenotypic evolution and contributes to hybrid incompatibilities between species. However, repetitive genomic regions are fragmented and misassembled in most contemporary genome assemblies. We generated highly contiguous de novo reference genomes for the species complex (, , and ), which speciated ∼250,000 yr ago. Our assemblies are comparable in contiguity and accuracy to the current genome, allowing us to directly compare repetitive sequences between these four species. We find that at least 15% of the complex species genomes fail to align uniquely to owing to structural divergence-twice the number of single-nucleotide substitutions. We also find rapid turnover of satellite DNA and extensive structural divergence in heterochromatic regions, whereas the euchromatic gene content is mostly conserved. Despite the overall preservation of gene synteny, euchromatin in each species has been shaped by clade- and species-specific inversions, transposable elements, expansions and contractions of satellite and tRNA tandem arrays, and gene duplications. We also find rapid divergence among Y-linked genes, including copy number variation and recent gene duplications from autosomes. Our assemblies provide a valuable resource for studying genome evolution and its consequences for phenotypic evolution in these genetic model species.
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http://dx.doi.org/10.1101/gr.263442.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919458PMC
March 2021

RBM3 Increases Cell Survival but Disrupts Tight Junction of Microvascular Endothelial Cells in Acute Lung Injury.

J Surg Res 2021 05 15;261:226-235. Epub 2021 Jan 15.

Laboratory of Anesthesiology, Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China. Electronic address:

Background: RNA-binding motif protein 3 (RBM3) is an important cold shock protein, which also responds to hypothermia or hypoxia. RBM3 is involved into multiple physiologic processes, such as promoting cell survival. However, its expression and function in acute lung injury (ALI) have not been reported.

Methods: A mouse ALI model was established by lipopolysaccharides (LPS) treatment. The RBM3 and cold inducible RNA-binding protein mRNA levels were examined by RT-qPCR, and MMP9 mRNA stability was determined by actinomycin D assay. RBM3 and MMP9 mRNA was tested by RNA immunoprecipitation (RIP assay). RBM3 overexpression or silent stable cell lines were established using recombinant lentivirus and subsequently used for cell survival and tight junction measurements.

Results: In this study, we found that RBM3, rather than cold inducible RNA-binding protein, was upregulated in lung tissue of ALI mice. RBM3 was increased in human pulmonary microvascular endothelial cells (HPMVECs) in response to LPS treatment, which is modulated by the NF-κB signaling pathway. Furthermore, RBM3 could reduce cell apoptosis induced by LPS, probably through suppressing p53 expression. Because increased permeability of HPMVECs leads to pulmonary edema in ALI, we subsequently examined the effect of RBM3 on cell tight junctions. Unexpectedly, RBM3 decreased the expression of tight junction protein zonula occludens-1 and increased cell permeability, and RBM3 overexpression increased MMP9 mRNA stability. Furthermore, RIP assay confirmed the interaction between RBM3 and MMP9 mRNA, possibly explaining the contribution of RBM3 to increase cell permeability.

Conclusions: RBM3 seems to act as a "double-edged sword" in ALI, that RBM3 alleviates cell apoptosis but increases HPMVEC permeability in ALI.
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http://dx.doi.org/10.1016/j.jss.2020.12.041DOI Listing
May 2021

Molecular Design Strategy for Simultaneously Strong Luminescence and High Mobility: Multichannel CH-π Interaction.

J Phys Chem Lett 2021 Jan 13;12(2):938-946. Epub 2021 Jan 13.

Department of Chemistry, Beijing Advanced Innovation Center for Imaging Theory and Technology Capital Normal University, Beijing 100048, China.

It is a big challenge to achieve high-performance organic semiconductor materials integrating both high luminescence efficiency and carrier mobility, because they are commonly regarded as a pair of contradiction. Here, combining a tight-binding model and density functional theory/time-dependent density functional theory, we propose a theoretical protocol to characterize the luminescence efficiency via an excitonic effective mass and charge transport ability via charge effective mass at the same level. Applying this protocol to a series of organic semiconductor materials, we find that the multichannel CH-π interaction can induce a heavy excitonic effective mass and light charge effective mass, which effectively balance the light-emitting efficiency and carrier mobility. Thus, a practical molecular design strategy is figured out to exploit novel organic semiconductor materials with strong luminescence and fast carrier transport simultaneously.
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http://dx.doi.org/10.1021/acs.jpclett.0c03453DOI Listing
January 2021

CIRP Sensitizes Cancer Cell Responses to Ionizing Radiation.

Radiat Res 2021 01;195(1):93-100

Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701.

Cold inducible RNA binding protein (CIRP), also named A18 hnRNP or CIRBP, is a cold-shock RNA-binding protein which can be induced upon various cellular stresses. Its expression level is induced in various cancer tissues relative to adjacent normal tissues; this is believed to play a critical role in cancer development and progression. In this study, we investigated the role of CIRP in cells exposed to ionizing radiation. Our data show that CIRP reduction causes cell colony formation and cell viability reduction after irradiation. In addition, CIRP knockdown cells demonstrated a higher DNA damage rate but less cell cycle arrest after irradiation. As a result, the induced DNA damage with less DNA repair processes led to an increased cell apoptosis rate in CIRP knockdown cells postirradiation. These findings suggest that CIRP is a critical protein in irradiated cells and can be used as a potential target for sensitizing cancer cells to radiation therapy.
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http://dx.doi.org/10.1667/RADE-20-00063.1DOI Listing
January 2021
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