Publications by authors named "Haibo Li"

460 Publications

Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145.

Transl Androl Urol 2021 Jun;10(6):2307-2319

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Background: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells .

Methods: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice.

Results: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014).

Conclusions: We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.
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http://dx.doi.org/10.21037/tau-20-1526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261405PMC
June 2021

Whole-exome sequencing identified a novel mutation in of a Chinese family.

J Genet 2021 ;100

Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China.

Choroideraemia (CHM) is a rare X-linked progressive-inherited retinal disease. In this study, we diagnosed and explored the genetic cause in a Chinese pedigree exhibiting nyctalopia and decreased visual acuity in early life. Clinical data and peripheral blood samples were collected from available family members. Sanger sequencing of and genes, and subsequently whole-exome sequencing was carried out to investigate the molecular cause. The proband was initially diagnosed as retinitis pigmentosa and experienced night blindness at an early age and decreased visual acuity in teens. The other affected males in this family suffered from the same problem. Direct sequencing failed to reveal the genetic cause and hence a novel hemizygous mutation c.861_862insGCTT was detected by WES in gene resulting in a premature stop codon and a truncated protein. Subsequently, it was confirmed by Sanger sequencing and cosegregation analysis. We describe a novel mutation c.861_862insGCTT in gene in a Chinese pedigree with choroideraemia. Our study emphasizes the utilization of next-generation sequencing in the diagnosis and genetic analysis of retinal diseases.
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January 2021

In-situ fabrication of few-layered MoS wrapped on TiO-decorated MXene as anode material for durable lithium-ion storage.

J Colloid Interface Sci 2021 Jul 6;604:30-38. Epub 2021 Jul 6.

Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai 200241, PR China. Electronic address:

Rational construction of hybrid materials integrating the collective virtues of individual building blocks has spurred significant interest in electrode materials for energy storage. Herein, a smart hybrid was fabricated via in-situ assembling of the few-layered MoS (f-MoS) coated on the multi-layered TiC MXene decorated with the TiO nanoparticles by the scalable hydrothermal and annealing approaches. In the unique architecture, the multi-layered TiC with the expanded interspaces as the conductive backbone can facilitate the electron transport, provide adequate space to facilitate the infiltration of organic electrolyte into the interior of electrode, and inhibit the aggregation of MoS nanosheets, while the f-MoS with enlarged interlayer can be beneficial for the lithium-ion diffusion and prevent the multi-layered TiCfrom restacking. Moreover, the TiO decorated on the TiC can effectively inhibit the instability of long-chain lithium polysulfides dissolved in organic electrolyte to improve the cycling stability. Thanks to the synergistic effect of the building blocks, the TiC/[email protected] hybrid employed as lithium storage anode delivers an extraordinary endurable ability with a high storage capacity of 403.1 mA h g after 1200 cycles at 2 A g. Importantly, the smart hybridization strategy in this work paves an efficient way to explore the high-performance MXene-based hybrid materials in energy storage fields.
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http://dx.doi.org/10.1016/j.jcis.2021.07.013DOI Listing
July 2021

Newborn Screening and Genetic Analysis Identify Six Novel Genetic Variants for Primary Carnitine Deficiency in Ningbo Area, China.

Front Genet 2021 24;12:686137. Epub 2021 Jun 24.

Department of Gynaecology, Ningbo Women and Children's Hospital, Ningbo, China.

Primary carnitine deficiency (PCD) is an autosomal recessive disorder that could result in sudden death. It is caused by a defect in the carnitine transporter encoded by (Solute Carrier Family 22 Member 5, MIM:603377). Currently, a number of variants in have been identified, however, the PCD prevalence and its variants in Ningbo area are unclear. In this study, we screened 265,524 newborns by using tandem mass spectrometry. Variants in were further detected by next-generation sequencing in individuals with abnormal free carnitine levels (C0). We identified 53 newborns with abnormal C0 levels and 26 with variants in Among them, 16 with compound heterozygous or homozygous variants in were diagnosed with PCD, suggesting the PCD birth prevalence in Ningbo city was 1/16,595. Moreover, the C0 level was significantly ( = 0.013) higher in PCD patients than in those with one variant. Besides, the c.1400C > G (p. S467C) and c.51C > G (p. F17L) variants were the most frequent and six novel variants are all predicted to be damaging. This study reports the largest PCD patients in Ningbo area by newborn screening and expands the variant spectrum of . Our findings demonstrate the clinical value of combining NBS program results with DNA analysis for the diagnosis of PCD.
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http://dx.doi.org/10.3389/fgene.2021.686137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264545PMC
June 2021

Synergistic Activity of Colistin Combined With Auranofin Against Colistin-Resistant Gram-Negative Bacteria.

Front Microbiol 2021 25;12:676414. Epub 2021 Jun 25.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Colistin-resistant (Col-R) bacteria are steadily increasing, and are extremely difficult to treat. New drugs or therapies are urgently needed to treat infections caused by these pathogens. Combination therapy with colistin and other old drugs, is an important way to restore the activity of colistin. This study aimed to investigate the activity of colistin in combination with the anti-rheumatic drug auranofin against Col-R Gram-negative bacteria. The results of checkerboard analysis demonstrated that auranofin synergized with colistin against Col-R Gram-negative bacteria. Time-kill assays showed significant synergistic antimicrobial activity of colistin combined with auranofin. Electron microscopy revealed that the combination resulted in more cellular structural alterations compared to each drug alone. Auranofin enhanced the therapeutic effectiveness of colistin in mouse peritoneal infection models. These results suggested that the combination of colistin and auranofin might be a potential alternative for the treatment of Col-R Gram-negative bacterial infections.
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http://dx.doi.org/10.3389/fmicb.2021.676414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267823PMC
June 2021

Near-unity blue-orange dual-emitting Mn-doped perovskite nanocrystals with metal alloying for efficient white light-emitting diodes.

J Colloid Interface Sci 2021 Jul 1;603:864-873. Epub 2021 Jul 1.

College of Physics, Jilin University, Changchun 130023, China. Electronic address:

The tunable dual-color emitting Mn doped CsPbClBr nanocrystals (NCs) with near-unity photoluminescence quantum yield (PL QY) were synthesized through post-treatment of metal bromide at room temperature for fabrication of efficient warm white light-emitting diodes (WLEDs). Especially, the CdBr treated blue-orange emitting Mn doped NCs with various Mn/Pb molar feed ratios exhibit higher PL QY of 97% and longer Mn PL lifetime of 0.9 ms. It is surprisingly found that the X-ray diffraction peak at 31.9° is almost not changed with increasing Br composition, meaning formation of metal alloying due to incorporation of amount of divalent cation in NCs. The strong and stable Mn PL at temperature ranging from 80 K to 360 K are revealed and the temperature-dependent energy transfer efficiencies in Mn doped CsPbClBr NCs are obtained. The enhancement mechanism of Mn PL QY was attributed to improved energy transfer from exciton to Mn d-d transition and suppressed defect state density after post-treatment. The efficient warm WLEDs with color rendering index of 90 and luminous efficacy of 92 lm/W at 10 mA were fabricated by combining blue-orange dual-emitting Mn doped [email protected] and green emissive [email protected] NCs with violet GaN chips.
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http://dx.doi.org/10.1016/j.jcis.2021.06.138DOI Listing
July 2021

YAP-Dependent Induction of CD47-Enriched Extracellular Vesicles Inhibits Dendritic Cell Activation and Ameliorates Hepatic Ischemia-Reperfusion Injury.

Oxid Med Cell Longev 2021 22;2021:6617345. Epub 2021 Jun 22.

Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatic ischemia-reperfusion injury (IRI) is the most common cause of liver damage leading to surgical failures in hepatectomy and liver transplantation. Extensive inflammatory reactions and oxidative responses are reported to be the major processes exacerbating IRI. The involvement of Yes-associated protein (YAP) in either process has been suggested, but the role and mechanism of YAP in IRI remain unclear. In this study, we constructed hepatocyte-specific YAP knockout (YAP-HKO) mice and induced a hepatic IRI model. Surprisingly, the amount of serum EVs decreased in YAP-HKO compared to WT mice during hepatic IRI. Then, we found that the activation of YAP increased EV secretion through F-actin by increasing membrane formation, while inhibiting the fusion of multivesicular body (MVB) and lysosomes in hepatocytes. Further, to explore the essential elements of YAP-induced EVs, we applied mass spectrometry and noticed CD47 was among the top targets highly expressed on hepatocyte-derived EVs. Thus, we enriched CD47 EVs by microbeads and applied the isolated CD47 EVs on IRI mice. We found ameliorated IRI symptoms after CD47 EV treatment in these mice, and CD47 EVs bound to CD172 on the surface of dendritic cells (DCs), which inhibited DC activation and the cascade of inflammatory responses. Our data showed that CD47-enriched EVs were released in a YAP-dependent manner by hepatocytes, which could inhibit DC activation and contribute to the amelioration of hepatic IRI. CD47 EVs could be a potential strategy for treating hepatic IRI.
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http://dx.doi.org/10.1155/2021/6617345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241504PMC
June 2021

Re-Du-Ning injection ameliorates LPS-induced lung injury through inhibiting neutrophil extracellular traps formation.

Phytomedicine 2021 Jun 19;90:153635. Epub 2021 Jun 19.

Institute of traditional Chinese medicine of Zhejiang Province, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, China. Electronic address:

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases and could occur in severe COVID-19 patients. Re-Du-Ning injection (RDN) is a tradition Chinese medicine preparation which has been clinically used for treatment of respiratory diseases including COVID-19.

Purpose: To elucidate the potential mechanisms of RDN for the treatment of ALI.

Methods: Female C57BL/6J mice were used to establish ALI model by intraperitoneal injection 10 mg/kg LPS, and RDN injection was intraperitoneally administered with the dose of 5 and 10 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to NETs were analyzed by ELISA, immunofluorescence, Western blotting and network pharmacological approach.

Results: RDN robustly alleviated LPS-induced ALI. Meanwhile, RDN downregulated the expression of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Specifically, RDN treatment inhibited the formation of neutrophil extracellular traps (NETs) and remarkably suppressed the protein of PAD4. The active compound from RDN decreased the phosphorylation of ERK1/2.

Conclusion: These findings demonstrate that RDN ameliorates LPS-induced ALI through suppressing MAPK pathway to inhibit the formation of NETs.
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http://dx.doi.org/10.1016/j.phymed.2021.153635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213523PMC
June 2021

Natural DNA-assisted RuP on highly graphitic N,P-codoped carbon for pH-wide hydrogen evolution.

Chem Commun (Camb) 2021 Jul 2;57(59):7284-7287. Epub 2021 Jul 2.

School of Chemistry and Chemical Engineering, Shandong Provincial Key Laboratory/Collaborative Innovation Center of Chemical Energy Storage & Novel Cell Technology, Liaocheng University, Liaocheng 252059, China.

Natural DNA was employed for the first time as a phosphorization agent and carbon source to controllably synthesize a RuP/N,P-codoped carbon composite by a simple "mix-and-pyrolyze" strategy, which displays higher activity for alkaline and acidic HER and neutral activity compared to Pt/C together with outstanding durability.
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http://dx.doi.org/10.1039/d1cc01951aDOI Listing
July 2021

Flexible Ultrasonic Patch for Accelerating Chronic Wound Healing.

Adv Healthc Mater 2021 Jul 1:e2100785. Epub 2021 Jul 1.

AML, Department of Engineering Mechanics, Tsinghua University, Beijing, 100084, China.

Ultrasound treatment is an effective method for accelerating chronic wound healing. However, it is not widely used because traditional ultrasonic probes cannot be conformal to the wound surface, which leads to limitations of use and unstable treatment effects. In addition, the use of liquid coupling agent increases the chance of wound infection. A strategy is proposed to design and fabricate a flexible ultrasonic patch for treating chronic wounds effectively. The piezoelectric ceramic in the patch is discretized into several linearly arranged units, which are integrated on a flexible circuit substrate. A thin hydrogel patch is used as both encapsulation and coupling layer to avoid wound infection and ensure the penetration of ultrasound. The ultrasonic patch is soft, light, and can completely conform to the treatment area. Bending of the patch focuses the sound beams on the center of the bending circle, which achieves control of the target treatment area. Ultrasound treatment experiments are carried out on some type-II diabetic rats. Immunohistochemical (IHC) results indicate that ultrasound accelerates wound healing by activating Rac1 in both dermal and epidermal layers. Treatment results show that wound treated with the ultrasound heals faster than wounds without. The healing time is shortened by ≈40%.
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http://dx.doi.org/10.1002/adhm.202100785DOI Listing
July 2021

High-Accuracy Surface Topography Manufacturing for Continuous Phase Plates Using an Atmospheric Pressure Plasma Jet.

Micromachines (Basel) 2021 Jun 10;12(6). Epub 2021 Jun 10.

Chengdu Fine Optical Engineering Research Center, Chengdu 610041, China.

The continuous phase plate (CPP) is the vital diffractive optical element involved in laser beam shaping and smoothing in high-power laser systems. The high gradients, small spatial periods, and complex features make it difficult to achieve high accuracy when manufacturing such systems. A high-accuracy and high-efficiency surface topography manufacturing method for CPP is presented in this paper. The atmospheric pressure plasma jet (APPJ) system is presented and the removal characteristics are studied to obtain the optimal processing parameters. An optimized iterative algorithm based on the dwell point matrix and a fast Fourier transform (FFT) is proposed to improve the accuracy and efficiency in the dwell time calculation process. A 120 mm × 120 mm CPP surface topography with a 1326.2 nm peak-to-valley (PV) value is fabricated with four iteration steps after approximately 1.6 h of plasma processing. The residual figure error between the prescribed surface topography and plasma-processed surface topography is 28.08 nm root mean square (RMS). The far-field distribution characteristic of the plasma-fabricated surface is analyzed, for which the energy radius deviation is 11 μm at 90% encircled energy. The experimental results demonstrates the potential of the APPJ approach for the manufacturing of complex surface topographies.
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http://dx.doi.org/10.3390/mi12060683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230669PMC
June 2021

Intelligent immune clonal optimization algorithm for pulmonary nodule classification.

Math Biosci Eng 2021 05;18(4):4146-4161

School of Electronic and Electrical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China.

Computer-aided diagnosis (CAD) of pulmonary nodules is an effective approach for early detection of lung cancers, and pulmonary nodule classification is one of the key issues in the CAD system. However, CAD has the problems of low accuracy and high false-positive rate (FPR) on pulmonary nodule classification. To solve these problems, a novel method using intelligent immune clonal selection and classification algorithm is proposed and developed in this work. First, according to the mechanism and characteristics of chaotic motion with a logistic mapping, the proposed method utilizes the characteristics of chaotic motion and selects the control factor of the optimal chaotic state, to generate an initial population with randomness and ergodicity. The singleness problem of the initial population of the immune algorithm was solved by the proposed method. Second, considering on the characteristics of Gaussian mutation operator (GMO) with a small scale, and Cauchy mutation operator (CMO) with a big scale, an intelligent mutation strategy is developed, and a novel control factor of the mutation is designed. Therefore, a Gauss-Cauchy hybrid mutation operator is designed. Ultimately, in this study, the intelligent immune clonal optimization algorithm is proposed and developed for pulmonary nodule classification. To verify its accuracy, the proposed method was used to analyze 90 CT scans with 652 nodules. The experimental results revealed that the proposed method had an accuracy of 97.87% and produced 1.52 false positives per scan (FPs/scan), indicating that the proposed method has high accuracy and low FPR.
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http://dx.doi.org/10.3934/mbe.2021208DOI Listing
May 2021

Perchlorate bioreduction in UASB reactor: S-autotrophic granular sludge formation and sulphate generation control.

Environ Technol 2021 Jul 9:1-11. Epub 2021 Jul 9.

School of Environmental and Municipal Engineering, Tianjin Key Laboratory of Aquatic Science and Technology, Tianjin Chengjian University, Tianjin, People's Republic of China.

Perchlorate () industrial wastewater requires efficient removal to prevent adverse environmental impacts, however, high concentration and low biodegradability give rise to poor bioreduction performance. -autotrophic granular sludge (-AuGS) was firstly cultivated for high concentration perchlorate () removal in the upflow anaerobic sludge blanket (UASB) reactor (: 150 mg L). Simultaneously, the was utilized to control the generation as electron donor, the effluent concentration (190 mg L) was satisfied with drinking water standard (250 mg L). Under the optimized condition of hydraulic retention time (HRT) (6 h) and / molar ratio (2.2), more EPS was secreted, which promoted the -AuGS formation and stability. Though acclimation of 146 d, the -AuGS was formed with a large average granular sludge size (612 μm) and an excellent settleability (sludge volume index: SVI/SVI= 1). With the mature -AuGS formation, the highest and loading was increased to 1.06 and 0.75 kg m d. Interestingly, , , and were the main microbial community in the -AuGS. This study proposed to form a novel -AuGS for developing the high concentration removal performance and to utilize the as an electron donor for controlling the excessive generation.
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http://dx.doi.org/10.1080/09593330.2021.1949046DOI Listing
July 2021

Exosomal ncRNAs profiling of mycobacterial infection identified miRNA-185-5p as a novel biomarker for tuberculosis.

Brief Bioinform 2021 Jun 25. Epub 2021 Jun 25.

Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: There are ever increasing researches implying that noncoded RNAs (ncRNAs) specifically circular RNAs (circRNAs) and microRNAs (miRNAs) in exosomes play vital roles in respiratory disease. However, the detailed mechanisms persist to be unclear in mycobacterial infection.

Methods: In order to detect circRNAs and miRNAs expression pattern and potential biological function in tuberculosis, we performed immense parallel sequencing for exosomal ncRNAs from THP-1-derived macrophages infected by Mycobacterium tuberculosis H37Ra, Mycobacterium bovis BCG and control Streptococcus pneumonia, respectively and uninfected normal cells. Besides, THP-1-derived macrophages were used to verify the validation of differential miRNAs, and monocytes from PBMCs and clinical plasma samples were used to further validate differentially expressed miR-185-5p.

Results: Many exosomal circRNAs and miRNAs associated with tuberculosis infection were recognized. Extensive enrichment analyses were performed to illustrate the major effects of altered ncRNAs expression. Moreover, the miRNA-mRNA and circRNA-miRNA networks were created and expected to reveal their interrelationship. Further, significant differentially expressed miRNAs based on Exo-BCG, Exo-Ra and Exo-Control, were evaluated, and the potential target mRNAs and function were analyzed. Eventually, miR-185-5p was collected as a promising potential biomarker for tuberculosis.

Conclusion: Our findings provide a new vision for exploring biological functions of ncRNAs in mycobacterial infection and screening novel potential biomarkers. To sum up, exosomal ncRNAs might represent useful functional biomarkers in tuberculosis pathogenesis and diagnosis.
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http://dx.doi.org/10.1093/bib/bbab210DOI Listing
June 2021

Incorporation of an Emissive CuI Core into Cross-Linked Networks: An Effective Strategy for Luminescent Organic-Inorganic Hybrid Coatings.

Inorg Chem 2021 Jun 22. Epub 2021 Jun 22.

School of Chemical Engineering and Technology, Sun Yat-Sen University, Zhuhai 519082, China.

Here, an effective strategy for the preparation of luminescent organic-inorganic hybrid coatings (OIHCs) by the incorporation of an emissive CuI core into cross-linked coating networks through coordination bonds is reported. The luminescent coatings obtained show potential application in a variety of areas, and such a synthetic strategy of the incorporation of an emissive inorganic core into extended networks has proven to be an efficient method for the synthesis of luminescent OIHCs.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00909DOI Listing
June 2021

Reduction of N to NH by TiO-supported Ni cluster catalysts: a DFT study.

Phys Chem Chem Phys 2021 May 25. Epub 2021 May 25.

Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L3G1, Canada.

Electrochemical techniques for ammonia synthesis are considered as an encouraging energy conversion technology to efficiently meet the challenge of nitrogen cycle balance. Herein, we find that TiO2(101)-supported Ni4 and Ni13 clusters can serve as efficient catalysts for electrocatalytic N2 reduction based on theoretical calculations. Electronic property calculations reveal the formation of electron-deficient Ni clusters on the TiO2 surface, which provides multiple active sites for N2 adsorption and activation. Theoretical calculation identifies the strongest activated configuration of N2* on the catalysts and confirms the potential-limiting step in the nitrogen reduction reaction (NRR). On Ni4-TiO2(101), N2* → NNH* is the potential-limiting step with a very small free energy increase (ΔG) of 0.24 eV (the corresponding overpotential is 0.33 V), while on Ni13-TiO2(101) the potential-limiting step occurs at NH* → NH2* with ΔG of 0.49 eV (the corresponding overpotential is 0.58 V). Moreover, the Nin-TiO2(101) catalyst, especially Ni13-TiO2(101), involves in a highly selective NRR even at the corresponding NRR overpotential. This work will enlighten material design to construct metal oxide supported transition metal clusters for the highly efficient NRR and NH3 synthesis.
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http://dx.doi.org/10.1039/d1cp00859eDOI Listing
May 2021

[Efficacy and safety of intravenous combined with topical administration of tranexamic acid in reducing blood loss after intramedullary fixation of intertrochanteric femoral fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 May;35(5):550-555

Department of Orthopaedics, West China-KongGang Hospital of Sichuan University (Chengdu Shuangliu District First People's Hospital), Chengdu Sichuan, 610200, P.R.China.

Objective: To investigate the efficacy and safety of intravenous combined with topical administration of tranexamic acid (TXA) in reducing blood loss after intramedullary fixation of intertrochanteric femoral fractures by a prospective controlled trial.

Methods: Patients with intertrochanteric femoral fractures, who were admitted for intramedullary fixation between June 2015 and July 2019, were selected as the study subjects, 120 of whom met the selection criteria. The patients were randomly assigned to 3 groups: intravenous administration group (group A, 41 cases), topical administration group (group B, 40 cases), and combined administrations group (group C, 39 cases). In group A, 4 patients occurred deep vein thrombosis of lower extremity before operation, 1 patient died of myocardial infarction on the 5th day after operation, and 1 patient developed severe pulmonary infection after operation. In group B, 2 patients occurred deep vein thrombosis of lower extremity before operation and 1 patient had iatrogenic fracture during operation. In group C, 3 patients occurred deep vein thrombosis of lower extremity before operation and 1 patient developed pulmonary infection before operation and gave up surgical treatment. All the above patients were excluded from the study, and the remaining 107 cases were included in the analysis, including 35, 37, and 35 cases in groups A, B, and C, respectively. There was no significant difference in gender, age, height, body mass, injury cause, fracture side and type, the interval between injury and operation, and preoperative hemoglobin (Hb), hematocrit between groups ( >0.05). Intraoperative TXA (15 mg/kg) was injected intravenously in group A at 30 minutes before operation, and 1 g of TXA was injected into the medullary cavity in group B after the proximal femur was grooted and before the intramedullary nail implantation, respectively. TXA was given in group C before and during operation according to the administration methods and dosage of groups A and B. Total blood loss, maximum Hb decrease, blood transfusion rate, operation time, fracture healing time, and the incidence of complications were recorded and compared between groups. The hip joint function were evaluated by Harris score.

Results: There was no significant difference in operation time between groups ( >0.05). The total blood loss, the maximum Hb decrease, and the blood transfusion rate in group B were the highest, followed by group A and group C, and the differences between groups were significant ( <0.05). No incision infection or pulmonary embolism occurred in the 3 groups after operation. The incidence of anemia in group C was significantly lower than that in groups A and B, the difference was significant ( <0.05). There was no significant difference in the incidence of subcutaneous hematoma, aseptic exudation, and deep vein thrombosis of lower extremity between groups ( >0.05). All patients in the 3 groups were followed up 8-35 months, with an average of 16.2 months. The fracture healing time of groups A, B, and C was (6.12±1.78), (5.89±1.63), and (5.94±1.69) months, respectively, and there was no significant difference between groups ( >0.05). At last follow-up, the Harris scores of the hip joints in groups A, B, and C were 83.18±7.76, 84.23±8.01, and 85.43±8.34, and the difference was not significant ( >0.05).

Conclusion: Preoperative intravenous injection combined with intraoperative topical application of TXA can effectively reduce blood loss and blood transfusion after intramedullary fixation of femoral intertrochanteric fracture, without increasing the risk of deep vein thrombosis, and the efficacy is better than that of intravenous injection or topical administration.
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http://dx.doi.org/10.7507/1002-1892.202010040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175210PMC
May 2021

Oxidation process of lead sulfide nanoparticle in the atmosphere or natural water and influence on toxicity toward Chlorella vulgaris.

J Hazard Mater 2021 09 8;417:126016. Epub 2021 May 8.

School of Resources and Civil Engineering, Northeastern University, Shenyang 110819, China. Electronic address:

Lead sulfide nanoparticle (nano-PbS) released into environment can cause hazards to human or ecosystem. Nano-PbS potentially undergoes oxidation in the environment, but oxidation mechanism is not understood yet. Herein, oxidation kinetics and products of nano-PbS by ozone (O), hydrogen peroxide (HO) and hydroxyl radical (HO·) in the atmosphere or natural water were investigated. Results show that oxidation process of nano-PbS can be divided into three stages, producing sulfate, ions and oxides of lead in sequence. O or HO·leads to faster release of ionic lead from nano-PbS in the initial stage than HO, but causes significant decrease of ionic lead by transforming divalent lead to tetravalent lead oxides in the second or third stage. Toxicity determined taking Chlorella Vulgaris as an example follows an order of PbO < PbO < nano-PbS < PbO < PbSO. Toxicity of lead particles is mainly determined by sizes influencing cellular uptake and solubility product constant (K) related with dissolution of lead in cells. The results indicate that the toxicity of nano-PbS increases in an initial oxidation stage and decreases in further oxidation stages. This study provides new insights into environmental behavior of nano-PbS and mechanism understandings for assessing ecological risks of nano-PbS.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126016DOI Listing
September 2021

Extracellular superoxide produced by Enterococcus faecalis reduces endometrial receptivity via inflammatory injury.

Am J Reprod Immunol 2021 May 15:e13453. Epub 2021 May 15.

Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity and Child Healthcare Hospital of Nantong University, Nantong, Jiangsu, China.

Problem: Chronic endometritis (CE) can cause infertility. Enterococcus faecalis is an opportunistic pathogen that is often found in the endometrium of CE patients. However, the mechanisms by which E. faecalis affects endometrial health are still unclear. In this study, we investigated the mechanism how extracellular superoxide produced by E. faecalis affected the endometrial receptivity.

Method Of Study: Superoxide production was blocked by deleting menB gene in E. faecalis OG1RF. Endometrial epithelial cells were infected by superoxide-producing E. faecalis OG1RF and superoxide-deficient strain WY84. Inflammatory cytokines, apoptosis, and biomarkers for the endometrial receptivity were analyzed.

Results: Infection of endometrial epithelial cells with superoxide-producing E. faecalis OG1RF induced expression of inflammatory cytokines, promoted apoptosis, and down-regulated expression of receptivity biomarkers compared to uninfected control. In contrast, superoxide-deficient E. faecalis WY84 had little effect on inflammatory cytokine production, apoptosis, and endometrial receptivity biomarkers.

Conclusions: Extracellular superoxide produced by E. faecalis is an important virulence factor for E. faecalis-induced endometritis leading to reduced receptivity of endometrial epithelial cells.
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http://dx.doi.org/10.1111/aji.13453DOI Listing
May 2021

[Study on newborn screening for Duchenne muscular dystrophy and diagnostic strategy].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 May;38(5):430-434

Ningbo Women and Children's Hospital, Ningbo Municipal Key Laboratory of Comprehensive Prevention and Treatment of Birth Defects, Ningbo, Zhejiang 315012, China.

Objective: To establish a newborn screening system for Duchenne muscular dystrophy (DMD) through assessment of MM isoenzyme of creatine kinase (CK-MM) activity.

Methods: The CK-MM level was detected using dry blood spot filter paper from 10 252 male newborns. The results were grouped based on their gestational age, sampling time and intervals between the experiments. The threshold value for CK-MM necessitating genetic testing was determined. Next-generation sequencing (NGS) was carried out for those with a CK-MM value over the threshold, and the result was verified by multiplex ligation-dependent probe amplification (MLPA).

Results: Based on the result of non-parametric rank sum test, the median CK-MM concentration has increased with the gestational age, and was inversely correlated with the age of the newborns among unaffected specimens. CK-MM on dry blood spot filter paper can be stable for 14 days at 2-8℃. Statistical analysis of CK-MM value of the 10 252 neonates suggested that the threshold may be set as 700 ng/mL. Exonic deletions were found in 2 confirmed cases, whose CK-MM level was greater than 2000 ng/mL.

Conclusion: Detection of CK-MM in dry blood spot filter paper has provided an effective method for newborn screening of DMD. This simple and inexpensive method can be used for large-scale screening, which is of great value to the early intervention and treatment of the disease.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200415-00270DOI Listing
May 2021

Compliant 3D frameworks instrumented with strain sensors for characterization of millimeter-scale engineered muscle tissues.

Proc Natl Acad Sci U S A 2021 May;118(19)

Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208;

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.
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http://dx.doi.org/10.1073/pnas.2100077118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126769PMC
May 2021

CaMK II -induced Drp1 phosphorylation contributes to blue light-induced AIF-mediated necroptosis in retinal R28 cells.

Biochem Biophys Res Commun 2021 Jun 30;559:113-120. Epub 2021 Apr 30.

Eye Center of Xiangya Hospital and Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, 410008, Hunan Province, China. Electronic address:

Retinal damage caused by blue light has become an important public health concern. Mitochondria have been found to play a key role in light-induced retinal cell death. In this study, we aimed to clarify the molecular mechanism involved in mitochondrion-related retinal cell damage caused by blue light, the major component of light-emitting diodes (LEDs). Our results show that blue light (450 nm, 300lux)-induced R28 cell death is caspase independent and can be attenuated by necrostatin-1. Apoptosis-inducing factor (AIF) cleavage and translocation to the nucleus are involved in the cell death progress. Blue light exposure causes mitochondrial fragmentation, which is mediated by phosphorylation at dynamin-related protein 1 (Drp1) Ser site, but it does not alter the protein levels of fission or fusion machinery. Knocking down Drp1 or treatment with Drp1 inhibitor Mdivi-1 protects R28 cells from blue light. Overproduction of reactive oxygen species (ROS) is induced by blue light. The ROS scavenger Trolox decreases Drp1 Ser phosphorylation level and mitochondrial fragmentation upon blue light exposure. Moreover, Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 blocks Drp1 phosphorylation and rescues mitochondrial fragmentation and AIF-mediated cell death caused by blue light. In conclusion, our data suggest that the CaMKII-Drp1 pathway plays a major role in blue light-induced AIF-mediated retinal cell damage.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.082DOI Listing
June 2021

Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation.

Mol Cytogenet 2021 Apr 26;14(1):22. Epub 2021 Apr 26.

Central Laboratory of Birth Defects Prevention and Control, Ningbo Women & Children's Hospital, Ningbo, 315000, Zhejiang, China.

Background: Aneuploidy is the most frequent cause of early-embryo abortion. Any defect in chromosome segregation would fail to satisfy the spindle assembly checkpoint (SAC) during mitosis, halting metaphase and causing aneuploidy. The mitotic checkpoint complex (MCC), comprising MAD1, MAD2, Cdc20, BUBR1 and BUB3, plays a vital role in SAC activation. Studies have confirmed that overexpression of MAD2 and BUBR1 can facilitate correct chromosome segregation and embryo stability. Research also proves that miR-125b negatively regulates MAD1 expression by binding to its 3'UTR. However, miR-125b, Mad1 and Bub3 gene expression in aneuploid embryos of spontaneous abortion has not been reported to date.

Methods: In this study, embryonic villi from miscarried pregnancies were collected and divided into two groups (aneuploidy and euploidy) based on High-throughput ligation-dependent probe amplification (HLPA) and Fluorescence in situ hybridization (FISH) analyses. RNA levels of miR-125b, MAD1 and BUB3 were detected by Quantitative real-time PCR (qRT-PCR); protein levels of MAD1 and BUB3 were analysed by Western blotting.

Results: statistical analysis (p < 0.05) showed that miR-125b and BUB3 were significantly down-regulated in the aneuploidy group compared to the control group and that MAD1 was significantly up-regulated. Additionally, the MAD1 protein level was significantly higher in aneuploidy abortion villus, but BUB3 protein was only mildly increased. Correlation analysis revealed that expression of MAD1 correlated negatively with miR-125b.

Conclusion: These results suggest that aneuploid abortion correlates positively with MAD1 overexpression, which might be caused by insufficient levels of miR-125b. Taken together, our findings first confirmed the negative regulatory mode between MAD1 and miR-125b, providing a basis for further mechanism researches in aneuploid abortion.
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http://dx.doi.org/10.1186/s13039-021-00538-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074413PMC
April 2021

Clinical applications of monitoring immune status with 90 immune cell subsets in human whole blood by 10-color flow cytometry.

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

Department of Pathology, Oregon Health and Science University, Portland, OR, USA.

Introduction: The immune system may involve and predict the different prognosis and therapy consequences. So, it's important to monitor and evaluate the immune status before and after treatments.

Methods: Flow cytometry is the best technology to perform immune monitoring, because it can detect immune cells using small amount of sample in a short time. The whole blood is the ideal sample for immune status monitoring, since it includes almost all the immune cells and it's relatively easy to obtain and less invasive than bone marrow or lymph node.

Results: Here we developed and validated a 10-color panel with only four tubes containing 29 antibodies to monitor 90 immune cell subsets in 2 ml whole blood samples. The major immune cell populations detected by our panel included T cell subsets (CD3 total T, Th, Tc, Treg, CD8 , CD8 , αβTCR, γδTCR, naïve, and memory T), T cell activation markers (CD25, CD69, and HLA-DR) and one immune checkpoint PD1, B cell subsets (B1, switched memory, non-switched, naïve B, and CD27 IgD B cells), neutrophils, basophils, four monocytic cell subsets, dendritic cells (pDCs and mDCs), and four NK cell subsets. These panels of antibodies had been applied to monitor immune status (percentage and absolute number) in total 303 cases with various diseases, such as leukemia (AML, CML, MM, and ALL), lymphoma (B cells and NK/T cells), cancers (colon, lung, prostate, and breast), immune deficiencies, and autoimmune diseases.

Conclusion: We provided proof of feasibility for clinical monitoring immune status and guiding immunotherapy by multicolor flow cytometry testing.
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http://dx.doi.org/10.1111/ijlh.13541DOI Listing
April 2021

LINC01123 enhances osteosarcoma cell growth by activating the Hedgehog pathway via the miR-516b-5p/Gli1 axis.

Cancer Sci 2021 Jun 7;112(6):2260-2271. Epub 2021 May 7.

Department of Orthopedics, Changzhou No.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, China.

The lncRNA LINC01123 has been reported to act as an oncogene in many human cancers. Nevertheless, the function and underlying mechanism of LINC01123 in osteosarcoma (OS) remain unclear. This study aimed to explore the roles and mechanisms of LINC01123 in OS progression. In this study, the expression of LINC01123 was significantly upregulated in OS cell lines than in a human osteoblast cell line. Furthermore, in vitro and in vivo experiments confirmed that knockdown of LINC01123 suppressed cell progression. Mechanistically, LINC01123 acted as a competing endogenous RNA by sponging miR-516b-5p, thus, increasing Gli1 expression by directly targeting its 3'UTR. Taken together, LINC01123 enhances OS proliferation and metastasis via the miR-516b-5p/Gli1 axis. Therefore, LINC01123 may be a potential therapeutic target for OS treatment.
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http://dx.doi.org/10.1111/cas.14913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177773PMC
June 2021

Dexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a/HO-1 signaling pathway.

Redox Biol 2021 05 21;41:101954. Epub 2021 Mar 21.

Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China. Electronic address:

Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed that preemptive administration of DEX (50μg/kg) alleviated lung pathologic injury, reduced oxidative stress indices (OSI), improved mitochondrial dysfunction, upregulated the expression of HIF-1α and HO-1, accompanied by shifting the dynamic course of mitochondria into fusion. Moreover, HO-1-knockout mice or HO-1 siRNA transfected NR8383 cells were pretreated with HIF-1α stabilizer DMOG and DEX to validate the effect of HIF-1a/HO-1 pathway on DEX-mediated mitochondrial dynamics in a model of endotoxin-induced lung injury. We found that pretreatment with DEX and DMOG distinctly relieved lung injury, decreased the levels of mitochondrial ROS and mtDNA, reduced OSI, increased nuclear accumulation of HIF-1a and HO-1 protein in wild type mice but not HO-1 KO mice. Similar observations were recapitulated in NC siRNA transfected NR8383 cells after LPS stimulation but not HO-1 siRNA transfected cells. Concertedly, DEX reversed the impaired mitochondrial morphology in LPS stimulated-wild type mice or NC siRNA transfected NR8383 cells, upregulated the expression of mitochondrial fusion protein, while downregulated the expression of fission protein in HIF-1a/HO-1 dependent pathway. Altogether, our data both in vivo and in vitro certified that DEX treatment ameliorated endotoxin-induced acute lung injury by preserving the dynamic equilibrium of mitochondrial fusion/fission through the regulation of HIF-1a/HO-1 signaling pathway.
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http://dx.doi.org/10.1016/j.redox.2021.101954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027777PMC
May 2021

Physiological, biochemical, and transcriptional regulation in a leguminous forage Trifolium pratense L. responding to silver ions.

Plant Physiol Biochem 2021 May 11;162:531-546. Epub 2021 Mar 11.

School of Resources and Civil Engineering, Northeastern University, 11 Wenhua Road, Heping District, Shenyang, 110819, China. Electronic address:

Trifolium pratense L. (red clover) is an important leguminous crop with great potential for Ag-contaminated environment remediation. Whereas, the molecular mechanisms of Ag tolerance in red clover are largely unknown. Red clover seedlings were used for physiological and transcriptomic investigation under 0, 20, 50, and 100 mg/L Ag stress in our research to reveal potential molecular resistance mechanism. Research showed that red clover possessed fairly strong Ag absorbance capacity, the Ag level reached 0.14 and 2.35 mg/g·FW in the leaves and roots under 100 mg/L AgNO stress condition. Root fresh weight, root dry weight, root water content, and photosynthetic pigments contents were significantly decreased with elevating AgNO concentration. Obvious withered plant tissue, microstructure disorder, and disrupted organelles were observed. In vitro evaluations (e.g., PI and DCFH-DA staining) represented that AgNO at high concentration (100 mg/L) exhibited obvious inhibition on cell viability, which was due possibly to the induction of reactive oxygen species (ROS) accumulation. A total of 44643 differentially expressed genes (DEGs) were identified under Ag stress, covering 27155 upregulated and 17488 downregulated genes. 12 stress-responsive DEGs was authenticated utilizing real-time quantitative PCR (qRT-PCR). Gene ontology (GO) analysis revealed that the DEGs were mostly related to metal ion binding (molecular function), nucleus (cellular component), and defense response (biological process). Involved DEGs in sequence-specific DNA binding transcription factor activity, response to various hormones (e.g., abscisic acid, IAA/Auxin, salicylic acid, and etc), calcium signal transduction, and protein ubiquitination were concluded to play crucial roles in Ag tolerance of red clover. On the other hand, Kyoto Encyclopedia of Genes and Genomes (KEGG) database annotated several stress responsive pathways such as plant-pathogen interaction, phenylpropanoid biosynthesis, ubiquitin mediated proteolysis, hormone signal transduction, and autophagy. Several down-regulated genes (e.g., RSF2, RCD1, DOX1, and etc) were identified indicating possible metabolic disturbance. Besides, protein-protein interaction network (PPI) identified several pivotal genes such as ribosomal proteins, TIR, and ZAT.
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http://dx.doi.org/10.1016/j.plaphy.2021.02.046DOI Listing
May 2021

Guizhi Fuling Capsule ameliorates endometrial hyperplasia through promoting p62-Keap1-NRF2-mediated ferroptosis.

J Ethnopharmacol 2021 Jun 24;274:114064. Epub 2021 Mar 24.

Department of Gynecology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, 310012, China; Center for Uterine Cancer Diagnosis & Therapy Research in Zhejiang Province, Hangzhou, 310012, China. Electronic address:

Ethnopharmacological Relevance: Guizhi Fuling Capsule (GFC) is a classical traditional Chinese medicine officially recorded in Synopsis of the Golden Chamber and has long been used to treat gynecological diseases in China. However, scientific evidence for the anti-endometrial hyperplasia potential of GFC used in traditional medicine is lacking.

Aim Of The Study: This study evaluated whether GFC protects against endometrial hyperplasia and its potential mechanism in mice.

Methods And Materials: We used estrogen (estradiol) to induce endometrial hyperplasia in mice. C57BL/6 mice were treated with estradiol subcutaneously for 21 days, and GFC (75 mg/kg and 150 mg/kg) was given intragastric administration from the first day of the modeling. H&E staining is used to evaluate endometrial tissue structure change. Malondialdehyde was measured to explore lipid peroxidation. Western blot, immunohistochemistry and immunofluorescence were performed to observe the expressions of GPX4, p62, Keap1 and NRF2.

Results: The degree of ferroptosis in endometrial tissue of patients with endometrial hyperplasia was lower than normal endometrial tissue. In addition, ferroptosis inducer imidazole ketone erastin could improve endometrial hyperplasia in mice. Interestingly, GFC significantly alleviated endometrial hyperplasia through triggering ferroptosis. Furthermore, GFC inhibited p62-Keap1-NRF2 pathway in estradiol-induced endometrial hyperplasia model.

Conclusions: GFC may attenuate estrogen-induced endometrial hyperplasia in mice through triggering ferroptosis via inhibiting p62-Keap1-NRF2 pathway. These findings suggest that GFC might act as a promising traditional Chinese medicine to treat endometrial hyperplasia.
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http://dx.doi.org/10.1016/j.jep.2021.114064DOI Listing
June 2021

The risk assessment model of fracture nonunion after intramedullary nailing for subtrochanteric femur fracture.

Medicine (Baltimore) 2021 Mar;100(12):e25274

Shuangliu District First People's Hospital, Chengdu, China.

Abstract: To investigate the influencing factors of fracture nonunion after intramedullary nailing for subtrochanteric fractures and to construct a risk assessment model.Based on the multicenter retrospective analysis of 251 patients, all patients were divided into modeling group and verification group. In the modeling group, postoperative fracture nonunion rate, general data, fracture-related factors, surgical reduction-related factors, mechanical and biological factors were calculated, and the influencing factors of fracture nonunion were screened by univariate analysis. Logistic regression model was used for multifactor analysis to construct the risk assessment model. Based on the logistic regression model, the risk prediction model was constructed by drawing the Nomogram diagram. Through the verification group, the influencing factors were evaluated again, and the differentiation and calibration of the model were evaluated. The calibration degree was evaluated by Hosmer-Lemeshow test, goodness of fit test, and calibration curve. The discriminant degree was evaluated by the receiver operating characteristic curve.Fracture nonunion occurred in 34 of 149 patients in the modeling group. Among the 14 potential influencing factors, univariate analysis and logistic regression analysis showed that postoperative hip varus, intramedullary nail fixation failure, and reduction of fracture with large incision were the risk factors of fracture nonunion. The medial cortex fracture was seen reduced on X-Ray was a protective factor for fracture nonunion, and a regression equation was established. Based on the logistic regression model, the Nomogram diagram is drawn. Twenty-four cases of fracture nonunion occurred in the verification group. The area under the receiver operating characteristic curve was area under curve =0.883 > 0.7, indicating that there was a moderate differentiation to evaluate the occurrence of fracture nonunion after operation. The goodness of fit test: the Hosmers-Lemeshow test (X2 = 2.921, P = .712 > .05) showed that the model had a good calibration.After intramedullary nailing of subtrochanteric fracture, hip varus, failure of intramedullary nail fixation and wide surgical dissection are the risk factors of fracture nonunion, and the postoperative reduction of medial cortex fracture is protective factor.National key research and development projects: 2016YFC0105806.
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http://dx.doi.org/10.1097/MD.0000000000025274DOI Listing
March 2021

Upregulation of SKA3 enhances cell proliferation and correlates with poor prognosis in hepatocellular carcinoma.

Oncol Rep 2021 04 24;45(4). Epub 2021 Mar 24.

Department of Hepatic Surgery (Liver Transplantation), The Third People's Hospital of Shenzhen (The Second Affiliated Hospital of Southern University of Science and Technology), Shenzhen, Guangdong 518000, P.R. China.

Hepatocellular carcinoma (HCC) is one of the most aggressive types of malignancy worldwide. However, the mechanism underlying its frequent recurrence remains unclear. Studies have demonstrated that spindle and kinetochore associated complex subunit 3 (SKA3) is highly expressed in colorectal and prostate cancer. The present study aimed to determine whether SKA3 could be a predictive and prognostic marker for liver cancer. SKA3 expression levels in liver cancer cell lines, liver cancer tissues, normal liver cells and non‑cancerous tissues were compared at both transcriptional and translational levels. Correlation between SKA3 levels, clinicopathological characteristics and patient survival was also assessed. Gene set enrichment analysis (GSEA) was performed to identify SKA3‑associated pathways. Furthermore, SKA3 was knocked down and overexpressed in liver cancer cells, and then assessed the effect on cell proliferation, cell cycle, and tumor formation ability. Kaplan‑Meier survival analysis and log‑rank test were used to evaluate the association between SKA3 expression levels and prognosis. SKA3 mRNA and protein expression levels were significantly higher in liver cancer cell lines and clinical samples, compared with normal controls. Immunohistochemical analysis of 110 patients revealed that upregulation of SKA3 correlated with clinical pathological characteristics and patient survival. GSEA showed that BENPORATH_PROLIFERATION gene set signaling pathways were correlated with SKA3 expression levels. Luciferase reporter activity assay revealed that knockdown of SKA3 significantly inhibited the activity of transcription factor E2F. Downregulation of SKA3 significantly inhibited cell proliferation, cell cycle arrest in G‑S phase and tumorigenesis both and , decreased the expression levels of cyclin D1 and phosphorylated‑-retinoblastoma and increased those of p21, suggesting a potential role of SKA3 in mediating tumor cell cycle and progression. SKA3 may function as an oncogene in liver cancer and may be a promising prognostic biomarker and candidate for targeted therapy.
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http://dx.doi.org/10.3892/or.2021.7999DOI Listing
April 2021
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