Publications by authors named "Ye Tian"

1,681 Publications

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CircRNAs: Decrypting the novel targets of fibrosis and aging.

Ageing Res Rev 2021 Jun 9:101390. Epub 2021 Jun 9.

Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, 710021, China. Electronic address:

Fibrosis is a typical aging-related pathological process involving almost all organs. It is usually initiated by organic injury and leads to the gradual decline of organ function or even loss. Circular RNAs (circRNAs) are being hailed as a newly rediscovered class of covalently closed transcripts without a 5' cap or 3' tail which draw increasing attention. In particular, circRNAs have been identified to be involved in the multifaceted processes of fibrosis in various organs, including the heart, liver, lung, and kidney. As more and more circRNAs are functionally characterized, they have become novel therapies for fibrosis. In this review, we systematically summarized current studies regarding the roles of circRNAs in fibrosis and shed light on the basis of circRNAs as a potential treatment for fibrosis.
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http://dx.doi.org/10.1016/j.arr.2021.101390DOI Listing
June 2021

SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells.

Eur J Pharmacol 2021 Jun 8:174236. Epub 2021 Jun 8.

Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an, China. Electronic address:

Ischemia reperfusion injury (IRI) is associated with poor prognoses in the setting of ischemic brain diseases. Silence information regulator 1 (SIRT1) is a member of the third class of nicotinamide adenine dinucleotide (NAD)-dependent sirtuins. Recently, the role of SIRT1/peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α) pathway in organ (especially the brain) protection under various pathological conditions has been widely investigated. Mangiferin (MGF), a natural C-glucosyl xanthone polyhydroxy polyphenol, has been shown to be beneficial to several nervous system diseases and the protective effects of MGF can be achieved through the regulation of SIRT1 signaling. This study is designed to investigate the protective effect of MGF treatment in the setting of cerebral IRI and to elucidate the potential mechanisms. We first evaluated the toxicity of MGF and chose the safe concentrations for the following experiments. MGF exerted obvious neuroprotection against hypoxia/reoxygenation (HR)-induced injury, indicated by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release and reactive oxygen species generation. MGF also restored the protein expressions of SIRT1, PGC-1α, Nrf2, NQO1, HO-1, NRF1, UCP2, and Bcl2 down-regulated by HR treatment. However, SIRT1 siRNA could reverse MGF-induced neuroprotection and decrease the expressions of molecules mentioned above. Taken together, our findings suggest that MGF treatment exerts neuroprotection against HR injury via activating SIRT1/PGC-1α signaling. These findings may provide a theoretical basis for the exploitation of MGF as a potential neuroprotective drug candidate, which may be beneficial for the ischemic stroke patients in clinic.
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http://dx.doi.org/10.1016/j.ejphar.2021.174236DOI Listing
June 2021

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

Lancet 2021 Jun 4. Epub 2021 Jun 4.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.

Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.

Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.

Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.

Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(21)01123-5DOI Listing
June 2021

Relationship Between C-reactive Protein and Risk of OSA in the Framework of Causal Inference.

Authors:
Tian Ye

Chest 2021 Jun;159(6):2515-2516

Department of Emergency Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2021.02.029DOI Listing
June 2021

Dysfunction of Synaptic Vesicle Endocytosis in Parkinson's Disease.

Front Integr Neurosci 2021 20;15:619160. Epub 2021 May 20.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including , , and , significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as , , , and also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.
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http://dx.doi.org/10.3389/fnint.2021.619160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172812PMC
May 2021

is a strong candidate gene in regulation of pork water-holding capacity.

Arch Anim Breed 2021 23;64(1):109-118. Epub 2021 Mar 23.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, PR China.

The UBX domain containing protein 1-like gene () promotes the degradation of myofibrillar proteins during meat maturation, which affects meat water-holding capacity (WHC). This study aims to identify functional mutations in promoter region, which affects the transcription activity and therefore the WHC. Firstly, we confirmed that the expression level was positively associated with WHC. Individuals with high and low WHC ( per group) were selected from 168 Duroc   Large White   Yorkshire (D   L   Y) crossbred pigs. The promoter region was comparatively sequenced using DNA pools from these two groups, and a mutation ca. 379T   G was revealed that had reverse allele distribution. The single nucleotide polymorphism (SNP) was then genotyped in the abovementioned population. TT genotype individuals exhibited higher mRNA level and higher WHC compared with GG genotype ones. Further luciferase assay confirmed that TT genotype promoter had higher activity. Moreover, the degradation of cytoskeletal framework proteins of muscle cells like , , , and was higher in TT genotype individuals than GG ones. In conclusion, we identified a SNP in the gene promoter that contributes to WHC improvement and pork quality. And is a strong candidate gene in regulation of pork WHC.
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http://dx.doi.org/10.5194/aab-64-109-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162240PMC
March 2021

Lobetyolin inhibits the proliferation of breast cancer cells ASCT2 down-regulation-induced apoptosis.

Hum Exp Toxicol 2021 Jun 2:9603271211021476. Epub 2021 Jun 2.

Department of Oncological Surgery, 74540The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 (), and were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 (), , and were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake down-regulating ASCT2. knockdown attenuated the anti-cancer effect of lobetyolin. knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect ASCT2 down-regulation-induced apoptosis in breast cancer cells.
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http://dx.doi.org/10.1177/09603271211021476DOI Listing
June 2021

DNA origami single crystals with Wulff shapes.

Nat Commun 2021 05 21;12(1):3011. Epub 2021 May 21.

National Laboratory of Solid State Microstructures, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, China.

DNA origami technology has proven to be an excellent tool for precisely manipulating molecules and colloidal elements in a three-dimensional manner. However, fabrication of single crystals with well-defined facets from highly programmable, complex DNA origami units is a great challenge. Here, we report the successful fabrication of DNA origami single crystals with Wulff shapes and high yield. By regulating the symmetries and binding modes of the DNA origami building blocks, the crystalline shapes can be designed and well-controlled. The single crystals are then used to induce precise growth of an ultrathin layer of silica on the edges, resulting in mechanically reinforced silica-DNA hybrid structures that preserve the details of the single crystals without distortion. The silica-infused microcrystals can be directly observed in the dry state, which allows meticulous analysis of the crystal facets and tomographic 3D reconstruction of the single crystals by high-resolution electron microscopy.
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http://dx.doi.org/10.1038/s41467-021-23332-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140131PMC
May 2021

Comparison of skeletal and soft tissue pericytes identifies CXCR4 bone forming mural cells in human tissues.

Bone Res 2020 May 22;8(1):22. Epub 2020 May 22.

Departments of Pathology, Johns Hopkins University, Baltimore, 21205, MD, USA.

Human osteogenic progenitors are not precisely defined, being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells (MSCs). Notably, select human pericytes can develop into bone-forming osteoblasts. Here, we sought to define the differentiation potential of CD146 human pericytes from skeletal and soft tissue sources, with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte. CD146CD31CD45 pericytes were derived by fluorescence-activated cell sorting from human periosteum, adipose, or dermal tissue. Periosteal CD146CD31CD45 cells retained canonical features of pericytes/MSC. Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo, while soft tissue pericytes did not readily. Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts, and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes. Conversely, enrichment of CXCR4 pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell. In sum, human skeletal and soft tissue pericytes differ in their basal abilities to form bone. Diversity exists in soft tissue pericytes, however, and CXCR4 pericytes represent an osteoblastogenic, non-adipocytic cell precursor. Indeed, enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.
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http://dx.doi.org/10.1038/s41413-020-0097-0DOI Listing
May 2020

[Establishment of Rat Prostatitis Model through Induction with Estrogen and Androgen at Different Concentrations].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 May;52(3):477-484

Department of Urologic Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550002 China.

Objective: To establish an experimental prostatitis animal model in Sprague-Dawley (SD) rats through induction by treatment of estrogen and androgen at different concentrations.

Methods: Fifty-three male SD rats aged 3 to 4 months were used in the study, and the castration model of male rats was established by excision of bilateral testes. The rats were randomly assigned to a blank group, a castration group and treatment groups receiving estrogen and androgen at different concentrations after castration, with 4 rats in each group. Dihydrotestosterone (DHT) and estradiol (E) were administered daily by subcutaneous injection to the treatment groups. All the rats were sacrificed by way of cervical dislocation after 1 month and the serum DHT and E concentrations of the rats in each group were assessed with ELISA. Prostate specimens were collected and the relative weight of the prostate of each group of rats was calculated. After HE staining of the prostate tissue, we observed with optic microscope structural changes in the prostate tissue and the state of prostatic inflammation in each group. Immunohistochemical examination was done to assess the expression of three inflammatory factors, transforming growth factor-β1 (TGF-β1), interleukin (IL)-6 and IL-8, in rat prostate tissues.

Results: The results of HE staining of rat prostate tissue showed that, compared with the blank group and castration group, the degree of inflammation increased significantly in the E0.05+DHT 0.5 mg/kg group and DHT0.15+E0.15 mg/kg group ( <0.05). However, once the concentration of DHT exceeded 0.5 mg/kg, the degree of inflammation did not further aggravate. The results of immunohistochemical staining showed that when the concentration of exogenous E was constant, the expression of TGF-β1 and IL-8 increased significantly in the E0.05+DHT 0.15 mg/kg group, E0.05+DHT 0.5 mg/kg group and E0.05+DHT 1.5 mg/kg group compared with that of the blank group ( <0.05). In the E0.05+DHT 0.15 mg/kg group and E0.05+DHT 0.5 mg/kg group, the expression of TGF-β1 and IL-8 increased significantly compared with that of the castration group ( <0.05). Once the concentration of DHT reached 0.5 mg/kg, further increase in the concentration of DHT did not lead to any significant changes in the expression of TGF-β1 or IL-8. In addition, when the concentration of exogenous DHT remained unchanged, the expressions of TGF-β1, IL-6, and IL-8 increased significantly in the DHT0.15+E 0.05 mg/kg group and DHT0.15+E 0.5 mg/kg group, compared with that of the blank group and castration group ( <0.05).

Conclusion: Castration combined with treatment of different concentrations of estrogen and androgen could successfully induce the prostatitis model in SD rats.
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http://dx.doi.org/10.12182/20210560305DOI Listing
May 2021

Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Cognitive Impairment Caused by Chronic Cerebral Hypoperfusion.

Mol Neurobiol 2021 May 17. Epub 2021 May 17.

National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) has beneficial effects in learning and memory. However, the mechanism by which PACAP improves cognitive impairment of vascular dementia (VaD) is not clear.

Methods: We established a VaD model by bilateral common carotid stenosis (BCAS) to investigate the molecular mechanism of cognitive impairment. Protein levels of PACAP, Sirtuin 3 (Sirt3), brain-derived neurotrophic factor (BDNF), and postsynaptic density 95 (PSD-95) were assessed by Western blot. In vitro, oxygen glucose deprivation (OGD) was used to simulate the ischemia/hypoxia state. HT22 cells were transfected with Sirt3 knockdown and overexpression to study the relationship between PACAP, Sirt3, and BDNF. In vivo, PACAP was administered intranasally to assess its protective effects on BCAS.

Results: The study showed that the levels of PACAP, Sirt3, BDNF, and PSD-95 were decreased in the BCAS model of VaD. PACAP increased the protein levels of Sirt3, BDNF, PSD-95, Bcl-2, and Bax under OGD condition in vitro. Sirt3 regulated BDNF and synaptic plasticity. Intranasal PACAP increased the protein levels of PAC1, Sirt3, BDNF, and PSD-95 in vivo.

Conclusions: This study provides evidence that PACAP regulates synaptic plasticity and plays an antiapoptotic role through Sirt3.
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http://dx.doi.org/10.1007/s12035-021-02381-2DOI Listing
May 2021

Modulation of solid surface with desirable under-liquid wettability based on molecular hydrophilic-lipophilic balance.

Chem Sci 2021 Mar 17;12(17):6136-6142. Epub 2021 Mar 17.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University Changchun 130012 P. R. China

There has been great interest in the fabrication of solid surfaces with desirable under-liquid wettability, and especially under-liquid dual-lyophobicity, because of their potential for widespread use. However, there remains the lack of a general principle to modulate the under-liquid wettability in terms of surface energy (SE). Herein, we found that the relative proportion between the polar and dispersive components in SE that reflects the competition between hydrophilicity and lipophilicity governs the under-liquid wettability of the solid surface. For the first time, we introduced hydrophilic-lipophilic balance (HLB) calculated solely based on the amount and type of hydrophilic and lipophilic fragments in surface molecules to rapidly predict the under-liquid wettability of a solid surface, thereby guiding the fabrication of solid surfaces with desirable under-liquid wettability. Accordingly, the under-liquid dual superlyophobic surfaces in a nonpolar oil-water-solid system were fabricated by grafting molecules with appropriate HLB values (, 6.341-7.673 in a cyclohexane-water-solid system) onto porous nanofibrous membranes, which were able to achieve continuous separation of oil-water mixtures. This work provides reasonable guidance for the fabrication of solid surfaces with targeted under-liquid wettability, which may lead to advanced applications in oil-water-solid systems.
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http://dx.doi.org/10.1039/d1sc00808kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098691PMC
March 2021

A γ-adducin cleavage fragment induces neurite deficits and synaptic dysfunction in Alzheimer's disease.

Prog Neurobiol 2021 May 13:102074. Epub 2021 May 13.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address:

Neurite deficits and synaptic dysfunction contribute to cognitive impairments in Alzheimer's disease (AD). However, the underlying molecular mechanisms remain unclear. Here, we show that γ-adducin, a cytoskeleton-associated protein that assembles the spectrin-actin framework, is cleaved by a lysosomal cysteine proteinase named asparagine endopeptidase (AEP). AEP is upregulated and activated during aging and cleaves γ-adducin at N357, disrupting spectrin-actin assembly. Moreover, γ-adducin (1-357) fragment downregulates the expression of Rac2, leading to defects in neurite outgrowth. Expression of the γ-adducin (1-357) fragment in the hippocampus of tau P301S transgenic mice resulted in significant AD-like pathology and cognitive deficits. In summary, AEP-mediated fragmentation of γ-adducin plays a vital role in AD. Blocking the activity of AEP might be a novel therapeutic target for AD.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102074DOI Listing
May 2021

Superamphiphilic TiO Composite Surface for Protein Antifouling.

Adv Mater 2021 May 13:e2003559. Epub 2021 May 13.

CAS Key Laboratory of Bio-Inspired Materials and Interface Sciences, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Unwanted protein adsorption deteriorates fouling processes and reduces analytical device performance. Wettability plays an important role in protein adsorption by affecting interactions between proteins and surfaces. However, the principles of protein adsorption are not completely understood, and surface coatings that exhibit resistance to protein adsorption and long-term stability still need to be developed. Here, a nanostructured superamphiphilic TiO composite (TiO /SiO ) coating that can effectively prevent nonspecific protein adsorption on water/solid interfaces is reported. The confined water on the superamphiphilic surface enables a low adhesion force and the formation of an energy barrier that plays a key role in preventing protein adsorption. This adaptive design protects the capillary wall from fouling in a harsh environment during the bioanalysis of capillary electrophoresis and is further extended to applications in multifunctional microfluidics for liquid transportation. This facile approach is not only perfectly applied in channels with complicated configurations but may also offer significant insights into the design of advanced superwetting materials to control biomolecule adhesion in biomedical devices, microfluidics, and biological assays.
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http://dx.doi.org/10.1002/adma.202003559DOI Listing
May 2021

Amino Acid Dependent Performance of Modified Chitosan Against Bacteria and Red Blood Cell.

J Nanosci Nanotechnol 2021 Nov;21(11):5443-5448

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry Chinese Academy of Sciences, Beijing 100190, China.

In order to combat antibiotic resistance, the development of new antibacterial agents is essential. In this study, we prepared four types of amino acid modified chitosan (CS-AA). Compared with chitosan modified with hydrophobic amino acids, the chitosan modified with positively charged amino acids showed higher antibacterial efficiency against under similar grafting rate. CS-AA achieves antibacterial properties mainly by destroying the integrity of bacterial cell membranes. All the four types of CS-AA show low toxicity towards red blood cells. This work indicates that positively charged groups are more important than hydrophobic groups in the design of chitosan-based antibacterial agents, and provides helpful information for the molecular design of effective antibacterial agents.
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http://dx.doi.org/10.1166/jnn.2021.19480DOI Listing
November 2021

Predictive Factors for Live Birth in Fresh Fertilization/Intracytoplasmic Sperm Injection Treatment in Poor Ovarian Reserve Patients Classified by the POSEIDON Criteria.

Front Endocrinol (Lausanne) 2021 12;12:630832. Epub 2021 Apr 12.

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into "expected" or "unexpected" groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age (OR 0.901; 95% CI 0.887~0.916; P < 0.001), body mass index (OR 0.963; 95% CI 0.951~0.982; P < 0.001), antral follicle counting (OR 1.049; 95% CI 1.009~1.042; P < 0.001) and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply (OR 0.7; 95% CI 0.7~0.8; P < 0.001). The inflection point of BMI was 23.4 kg/m, and BMI had a negative correlation with live birth (OR 0.963; 95% CI 0.951~0.982; P < 0.001). The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.
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http://dx.doi.org/10.3389/fendo.2021.630832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099421PMC
April 2021

Identification of autophagy-related genes signature predicts chemotherapeutic and immunotherapeutic efficiency in bladder cancer (BLCA).

J Cell Mol Med 2021 Jun 7;25(12):5417-5433. Epub 2021 May 7.

Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.

Autophagy maintains cellular homeostasis by degrading and recycling cytoplasmic components under stress conditions, which is identified to be involved in tumorigenesis and now has been recognized as novel target in cancer treatment. In present study, we gathered total autophagy-related genes and established an autophagy-related genes signature (ATGRS) through LASSO cox regression analysis in BLCA. Kaplan-Meier survival and multivariate cox regression analyses both showed the ATGRS was a robust independent prognostic factor with high accuracy. Subsequently, integrated analyses indicated that ATGRS had a strong correlation with molecular subtypes, clinicopathological characteristics and somatic mutation alteration. Moreover, ATGRS was found to be positively correlated with the infiltration of immune cells in tumour microenvironment (TME) and immune checkpoint expression, indicating the potent role of autophagy by regulating the TME. In addition, ATGRS was proved to be efficient in predicting the clinical benefit of immune checkpoint inhibitors (ICIs) based immunotherapy and chemotherapy in BLCA. Furthermore, we observed abnormal expression levels of autophagy-related genes and found the different behaviour of ATGRS in pancancer by LASSO cox regression analysis. Therefore, construction of ATGRS in BLCA could help us to interpret the underlying mechanism of autophagy and sheds a light on the clinical application for a combination of autophagy modification with targeted immunotherapy and chemotherapy in BLCA.
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http://dx.doi.org/10.1111/jcmm.16552DOI Listing
June 2021

Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels.

J Biol Chem 2021 May 3:100738. Epub 2021 May 3.

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong; Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong; State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong; HKUST Shenzhen Research Institute, Hong Kong University of Science and Technology, Hong Kong; Hong Kong Branch of Guangdong Southern Marine Science and Engineering Laboratory (Guangzhou), Hong Kong University of Science and Technology, Hong Kong. Electronic address:

ANO1 (TMEM16A) is a calcium-activated chloride channel that plays critical roles in diverse physiological processes, such as sensory transduction and epithelial secretion. ANO1 levels have been shown to be altered under physiological and pathological conditions, although the molecular mechanisms that control ANO1 protein levels remain unclear. The ubiquitin-proteasome system is known to regulate the levels of numerous ion channels, but little information is available regarding whether and how ubiquitination regulates levels of ANO1. Here, we showed that two E3 ligases, TRIM23 and TRIM21, physically interact with the C-terminus of ANO1. In vitro and in vivo assays demonstrated that whereas TRIM23 ubiquitinated ANO1 leading to its stabilization, TRIM21 ubiquitinated ANO1 and induced its degradation. Notably, ANO1 regulation by TRIM23 and TRIM21 is involved in chemical-induced pain sensation, salivary secretion, and heart-rate control in mice, and TRIM23 also mediates ANO1 upregulation induced by epidermal growth factor (EGF) treatment. Our results suggest that these two antagonistic E3 ligases act together to control ANO1 expression and function. Our findings reveal a previously unrecognized mechanism for regulating ANO1 protein levels and identify a potential molecular link between ANO1 regulation, EGF, and other signaling pathways.
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http://dx.doi.org/10.1016/j.jbc.2021.100738DOI Listing
May 2021

Transferrin receptor 1 ablation in satellite cells impedes skeletal muscle regeneration through activation of ferroptosis.

J Cachexia Sarcopenia Muscle 2021 Jun 6;12(3):746-768. Epub 2021 May 6.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Background: Satellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle-specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored.

Methods: RNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1 and Tfr1 (n = 6-8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects.

Results: By comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P < 0.005), so as to its protein level in SCs of aged mice. From in vivo and ex vivo experiments, Tfr1 deletion in SCs results in an irreversible depletion of SCs (~60% reduction, P < 0.005) and cell-autonomous defect in SC proliferation and differentiation, leading to skeletal muscle regeneration impairment, followed by labile iron accumulation, lipogenesis, and decreased Gpx4 and Nrf2 protein levels leading to reactive oxygen species scavenger defects. These abnormal phenomena including iron accumulation, activation of unsaturated fatty acid biosynthesis, and lipid peroxidation are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis further exacerbates SC proliferation and skeletal muscle regeneration. Ferrostatin-1, a ferroptosis inhibitor, could not rescue ferroptosis. However, intramuscular administration of lentivirus-expressing Tfr1 could partially reduce labile iron accumulation, decrease lipogenesis, and promote skeletal muscle regeneration. Most importantly, declined Tfr1 but increased Slc39a14 protein level on cellular membrane contributes to labile iron accumulation in skeletal muscle of aged rodents (~80 weeks old), leading to activation of ferroptosis in aged skeletal muscle. This is inhibited by ferrostatin-1 to improve running time (P = 0.0257) and distance (P = 0.0248).

Conclusions: Satellite cell-specific deletion of Tfr1 impairs skeletal muscle regeneration with activation of ferroptosis. This phenomenon is recapitulated in skeletal muscle of aged rodents and human sarcopenia. Our study provides mechanistic information for developing novel therapeutic strategies against muscular ageing and diseases.
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http://dx.doi.org/10.1002/jcsm.12700DOI Listing
June 2021

Discovery of 4-Arylindolines Containing a Thiazole Moiety as Potential Antitumor Agents Inhibiting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction.

J Med Chem 2021 05 3;64(9):5519-5534. Epub 2021 May 3.

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.

Through specific structural modification of a 4-phenylindoline precursor, new 4-arylindolines containing a thiazole moiety were developed and found to be promising modulators of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. Compound exhibited outstanding biochemical activity, with an IC of 11.2 nM in a homogeneous time-resolved fluorescence assay. In the cell-based assay, significantly promoted IFN-γ secretion and rescued T-cell proliferation, which were inhibited by PD-1 activation. Furthermore, showed favorable antitumor activity in a mouse 4T1 breast carcinoma model. Moreover, in mouse CT26 colon carcinoma models, potently suppressed the growth of CT26/PD-L1 tumor but did not obviously affect the growth of CT26/vector tumor. The results of flow cytometry analysis indicated that inhibited tumor growth by activating the immune microenvironment. We concluded that is a new starting point for further development of PD-1/PD-L1 interaction inhibitors as antitumor agents.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01958DOI Listing
May 2021

By Regulating the NLRP3 Inflammasome Can Reduce the Release of Inflammatory Factors in the Co-Culture Model of Tuberculosis H37Ra Strain and Rat Microglia.

Front Cell Infect Microbiol 2021 13;11:637769. Epub 2021 Apr 13.

The College of Life Sciences and Medicine, Northwest University, Xi'an, China.

Objective: Tuberculosis infection of the Central Nervous System can cause severe inflammation in microglia, and NLRP3 inflammasome is also an important source of inflammation in microglia. Therefore, in this study, we used a co-culture model of rat microglia and tuberculosis H37Ra strain to explore the influence of tuberculosis infection on the NLRP3 inflammasome in microglia and its regulation mechanism.

Methods: We cultured primary microglia from SD rats and co-cultured with tuberculosis H37Ra strain for 4 hours to establish a co-culture model. At the same time, MCC950, Z-YVAD-FMK, BAY-11-7082, Dexamethasone, RU486, BzATP, BBG and extracellular high potassium environment were used to intervene the co-cultivation process. Subsequently, western blot, real-time PCR, ELISA and other methods were used to detect the changes of NLRP3 inflammasome-related molecules in microglia.

Results: After co-cultivation, the NLRP3 inflammasomes in microglia were activated and released a large amount of IL-18 and IL-1β. By regulating NLRP3 inflammasome complex, caspase-1, NF-κB and P2X7R during the co-culture process, it could effectively reduce the release of IL-18 and IL-1β, and the mortality of microglia.

Conclusion: Our results indicate that the NLRP3 inflammasome pathway is an important part of the inflammatory response of microglia caused by tuberculosis infection. By intervening the NLRP3 inflammasome pathway, it can significantly reduce the inflammatory response and mortality of microglia during the tuberculosis H37Ra strain infection. This research can help us further understand the inflammatory response mechanism of the central nervous system during tuberculosis infection and improve its treatment.
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http://dx.doi.org/10.3389/fcimb.2021.637769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078893PMC
April 2021

Association of Polyvascular Disease and Elevated Interleukin-6 With Outcomes in Acute Ischemic Stroke or Transient Ischemic Attack.

Front Neurol 2021 13;12:661779. Epub 2021 Apr 13.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Polyvascular disease (PolyVD) and interleukin (IL)-6 are associated with poor outcomes in patients with stroke respectively. However, whether combined PolyVD and elevated IL-6 levels would increase the risk of poor outcomes of stroke patients is yet unclear. Data were obtained from the Third China National Stroke Registry (CNSR-III). PolyVD was defined as acute ischemic stroke (AIS) or transient ischemic attack (TIA) with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Patients were divided into four groups according to the combination of vascular beds number (non-PolyVD or PolyVD) and IL-6 levels (IL-6 < 2.64 pg/mL or IL-6 ≥ 2.64 pg/mL). The primary outcome was a recurrent stroke at 1-year follow-up. Cox proportional hazard models were employed to identify the association of the combined effect of PolyVD and IL-6 with the prognosis of patients. A total of 10,773 patients with IL-6 levels and 1-year follow-up were included. The cumulative incidence of recurrent stroke was 9.87% during the 1-year follow-up. Compared to non-PolyVD and IL-6<2.64 pg/mL patients, patients had non-PolyVD with IL-6 ≥ 2.64 pg/mL (HR 1.245 95%CI 1.072-1.446; < 0.001) and PolyVD with IL-6 <2.64 pg/mL (HR 1.251 95%CI 1.002-1.563; = 0.04) were associated with an increased risk of recurrent stroke during 1-year follow-up. Likewise, patients with PolyVD and IL-6 ≥ 2.64 pg/mL (HR 1.290; 95% CI 1.058-1.572; = 0.01) had the highest risk of recurrent stroke at 1-year follow-up among groups. PolyVD and elevated IL-6 levels are both associated with poor outcomes in patients with AIS or TIA. Moreover, the combination of them increases the efficiency of stroke risk stratification compared with when used alone. More attention and intensive treatment should be given to those patients with both PolyVD and elevated IL-6 levels.
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http://dx.doi.org/10.3389/fneur.2021.661779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076541PMC
April 2021

Emission Variations of Primary Air Pollutants from Highway Vehicles and Implications during the COVID-19 Pandemic in Beijing, China.

Int J Environ Res Public Health 2021 04 12;18(8). Epub 2021 Apr 12.

Beijing Municipal Ecology and Environment Bureau, Beijing 100048, China.

According to the traffic flow variation from January 2019 to August 2020, emissions of primary air pollutants from highway vehicles were calculated based on the emission factor method, which integrated the actual structure of on-road vehicles. The characteristics of on-highway traffic flow and pollution emissions were compared during various progression stages of coronavirus disease (COVID-19). The results showed that the average daily traffic volume decreased by 38.2% in 2020, with a decrease of 62% during the strict lockdown due to the impact of COVID-19. The daily emissions of primary atmospheric pollutants decreased by 29.2% in 2020 compared to the same period in 2019. As for the structure of on-highway vehicle types, the small and medium-sized passenger vehicles predominated, which accounted for 76.3% of traffic, while trucks and large passenger vehicles accounted for 19.7% and 4.0%, but contributed 58.4% and 33.9% of nitrogen oxide (NO) emissions, respectively. According to the simulation results of the ADMS model, the average concentrations of NO were reduced by 12.0 µg/m compared with the same period in 2019. As for the implication for future pollution control, it is necessary to further optimize the structure of on-highway and the road traffic vehicle types and increase the proportions of new-energy vehicles and vehicles with high emission standards.
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http://dx.doi.org/10.3390/ijerph18084019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070592PMC
April 2021

Functional Characterization of a Sugar Beet Transcription Factor in Salt Stress Tolerance.

Int J Mol Sci 2021 Apr 1;22(7). Epub 2021 Apr 1.

Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education, Heilongjiang University, Harbin 150080, China.

The basic/helix-loop-helix (bHLH) transcription factor (TF) plays an important role for plant growth, development, and stress responses. Previously, proteomics of NaCl treated sugar beet leaves revealed that a bHLH TF, , was significantly increased under salt stress. The BvbHLH93 protein localized in the nucleus and exhibited activation activity. The expression of was significantly up-regulated in roots and leaves by salt stress, and the highest expression level in roots and leaves was 24 and 48 h after salt stress, respectively. Furthermore, constitutive expression of conferred enhanced salt tolerance in as indicated by longer roots and higher content of chlorophyll than wild type. Additionally, the ectopic expression lines accumulated less Na and MDA, but more K than the WT. Overexpression of the enhanced the activities of antioxidant enzymes by positively regulating the expression of antioxidant genes and . Compared to WT, the overexpression plants also had low expression levels of and , which are involved in reactive oxygen species (ROS) production. These results suggest that plays a key role in enhancing salt stress tolerance by enhancing antioxidant enzymes and decreasing ROS generation.
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http://dx.doi.org/10.3390/ijms22073669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037259PMC
April 2021

Bioinspired Fibers with Controlled Wettability: From Spinning to Application.

ACS Nano 2021 05 28;15(5):7907-7930. Epub 2021 Apr 28.

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong 999077, China.

Our knowledge on spider silks shows the importance of joining heterogeneous structures and surface chemical compositions in preparing fibers, fibrous surfaces, and 3D materials with a controllable wettability. We start our review with spider silk and proceed to the historical development of nature-inspired spinning processes, their products, and their advantages and disadvantages. Relevant wetting states are then summarized in fiber-based systems. Recent applications are reviewed, including one-dimensional spindle-knotted fibers for highly efficient fog harvesting, long-distance transport, and stimulus-responsive wettability and two-dimensional spindle-knotted fibrous systems for water collection, functional surfaces, and filtration. Finally, we offer some perspective on future research trends regarding biomimetic fibers for wetting-controlled engineering.
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http://dx.doi.org/10.1021/acsnano.0c08898DOI Listing
May 2021

The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin.

J Ethnopharmacol 2021 Jul 20;275:114133. Epub 2021 Apr 20.

Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China. Electronic address:

Ethnopharmacological Relevance: Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia.

Aim Of The Study: In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated.

Materials And Methods: First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs.

Results: This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo.

Conclusion: These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic.
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http://dx.doi.org/10.1016/j.jep.2021.114133DOI Listing
July 2021

Microchannel and Nanofiber Array Morphology Enhanced Rapid Superspreading on Animals' Corneas.

Adv Mater 2021 Jun 23;33(23):e2007152. Epub 2021 Apr 23.

Key Laboratory of Bioinspired Smart Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

The dynamic spreading phenomenon of liquids is vital for both understanding wetting mechanisms and visual reaction time-related applications. However, how to control and accelerate the spreading process is still an enormous challenge. Here, a unique microchannel and nanofiber array morphology enhanced rapid superspreading (RSS) effect on animals' corneas with a superspreading time (ST) of 830 ms is found, and the respective roles of the nanofiber array and the microchannel in the RSS effect are explicitly demonstrated. Specifically, the superspreading is induced by in-/out-of-plane nanocapillary forces among the nanofiber array; the microchannel is responsible for tremendously speeding up the superspreading process. Inspired by the RSS strategy, not only is an RSS surface fabricated with an ST of only 450 ms, which is, respectively, more than 26 and 1.8 times faster than conventional superamphiphilic surfaces and animal's corneas and can be applied as RSS surfaces on video monitors to record clear videos, but also it is demonstrated that the RSS effect has tremendous potential as advanced ophthalmic material surfaces to enhance its biocompatibility for clear vision.
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http://dx.doi.org/10.1002/adma.202007152DOI Listing
June 2021

An effective oxygen content detection in phosphorescence of PtOEP-C6/Poly (St-co-TFEMA).

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 19;257:119786. Epub 2021 Apr 19.

Division of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.

The phosphorescence of PtOEP-C6/Poly (St-co-TFEMA) has been investigated to achieve an accurate oxygen content, which is always puzzled as its extreme temperature sensitivity. The relations of oxygen content and phosphorescence intensity ratio can be perfectly fitted by the Stern-Volmer equation at different temperatures, meanwhile the monotonic quenching constant K is obtained, which enables us to develop a method of temperature correction to realize the intrinsic oxygen content. Then a clear fundamental picture of the temperature quenching mechanism of PtOEP is drawn by the time-resolved spectroscopy, the temperature sensitivity of phosphorescence arises from the enhanced quenching effect of oxygen by temperature. Our results provide an effective method to gain accurate oxygen content by simple optical measurement.
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http://dx.doi.org/10.1016/j.saa.2021.119786DOI Listing
August 2021

A case of extramedullary T-lymphoblastic blast crisis as an initial presentation of chronic myelogenous leukemia.

Int J Lab Hematol 2021 Apr 18. Epub 2021 Apr 18.

Department of Hematology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

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http://dx.doi.org/10.1111/ijlh.13545DOI Listing
April 2021

A novel NCOR2-NTRK1 fusion detected in a patient of lung adenocarcinoma and response to larotrectinib: a case report.

BMC Pulm Med 2021 Apr 17;21(1):125. Epub 2021 Apr 17.

Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, 4 Chongshan East Road, Shenyang, 110032, Liaoning, People's Republic of China.

Background: The identification of NTRK fusions in tumours has become critically important due to the actionable events predictive of response to TRK inhibitor. It is not clear whether the NTRK breakpoint location is different for response to targeted therapy and NTRK fusions affects the efficacy of immunotherapy.

Case Presentation: Here we reported a 60-year-old female diagnosed with advanced lung adenocarcinoma. NGS-based molecular profiling identified a novel NCOR2-NTRK1 fusion and high tumor mutational burden (TMB) (58.58 mutations/Mb) in this case. Additionally, program death-ligand 1 (PD-L1) expression was detected in 20-30% of the tumor cells by immunohistochemical (IHC) staining. The patient received treatment with anti-PD-1 immune checkpoint inhibitor of camrelizumab. After two cycles of treatment, the CT scan showed some tumor nodules were still enlarged, indicating disease progression. She was then changed to TRK inhibitor larotrectinib. One month later, the CT scan showed the volume of some lesions started to decrease, and no metastasis lesions were found. The patient then continued the administration of larotrectinib, and some lesion sizes were significantly reduced or even disappeared in the next few months. Currently, this patient is still alive.

Conclusions: Altogether, this report provided a new driver of lung adenocarcinoma expanded the mutational spectrum of NTRK1 fusion variants and suggested using larotrectinib as the targeted therapy is more effective than anti-PD-1 inhibitor in lung adenocarcinoma harboring with NTRK fusion, positive PD-L1 expression, and high TMB simultaneously.
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http://dx.doi.org/10.1186/s12890-021-01490-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052639PMC
April 2021