Publications by authors named "Xudong Wang"

651 Publications

Exploring the Potentials of TiCNT ( = 0, 1, 2)-MXene for Anode Materials of High-Performance Sodium-Ion Batteries.

ACS Appl Mater Interfaces 2021 May 7. Epub 2021 May 7.

School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, China.

Two-dimensional (2D) MXenes, including carbides, nitrides, and carbonitrides MXene, have been proved to be a possible candidate as anode materials of sodium-ion batteries. This paper focuses on the electronic properties and the electrochemical performance of nitrides MXene. First, density functional theory simulations were utilized to disclose the geometric structure and electronic properties, Na diffusion path, and storage behaviors of titanium carbonitrides TiCNT, nitrides MXene TiNT, and carbides MXene TiCT with oxygen terminations, predicting the more excellent performance of TiNO than TiCO. Also, then the structure characterization and electrochemical performance experiments of TiCT and TiCNT were conducted to verify the theoretical predictions and test the cycling performances. The superior performance of TiNO originates from the stronger connection of O-Ti-N than that of O-Ti-C, resulting in the stackings of TiNO being tighter and the interlayer spacings being larger than that of TiCO, which is advantageous to sodiation and desodiation. The capacity of TiCNT increased again to 145 mAh/g after 35 cycles at a current density of 20 mA/g, which demonstrated a better rate performance than TiCT corroborated by the diffusion barriers of the theoretical calculation results. TiCNT exhibits a good cycling performance of 110 mAh/g (≈60% of the initial value) after 200 cycles, which is better than that of 87 mAh/g (≈51% of the initial value) of TiCT. It is worth noting that all these performances ensure that nitride MXene is more suitable as the anode material of Na-ion batteries than carbide MXene. These findings are conducive to expanding the MXene family and promoting their application in energy storage applications.
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http://dx.doi.org/10.1021/acsami.1c02470DOI Listing
May 2021

Identifying the fouling behavior of forward osmosis membranes exposed to different inorganic components with high ionic strength.

Environ Sci Pollut Res Int 2021 May 4. Epub 2021 May 4.

Research Institute of Membrane Separation Technology of Shaanxi Province, Key Laboratory of Membrane Separation of Shaanxi Province, Key Laboratory of Northwest Water Resources, Environmental and Ecology, Ministry of Education, Key Laboratory of Environmental Engineering, Shaanxi Province, School of Environmental & Municipal Engineering, Xi'an University of Architecture and Technology, Yan Ta Road. No.13, Xi'an, 710055, China.

Functionalized multiwalled carbon nanotube (f-MWCNT) mixed matrix forward osmosis (FO) membranes were fabricated by phase inversion, and the mechanism of sodium alginate (SA) membrane fouling in the presence of various inorganic components with high ionic strength was thoroughly investigated. The membrane incorporated with 0.5% f-MWCNTs (M-0.5) exhibited enhanced performance, which was attributed to the hydrophilicity of the modified nanoparticles and their good compatibility with the cellulose acetate (CA) substrate. Moreover, it was found that the initial permeate flux decline rate for all FO membranes investigated followed the order Na + Ca + Mg > Na + Ca > Na + Mg > Na, which was attributed to the particle size of SA macromolecules in the corresponding solutions. However, the gradual change in attenuation was consistent with adhesion force observations made for the SA-fouled FO membrane in the later steady-state stage, and there was little difference among M-0 (without f-MWCNTs), M-0.5, and M-1 (with 1% f-MWCNTs). Furthermore, the SA adsorption layer was most compact in the presence of Ca, and the flux recovery rate (FRR) was the lowest after simple hydraulic cleaning, but the overall FRRs for FO membranes were greater than 85%. This implies that although a decrease in electrostatic repulsion leads to the formation of a compact fouling layer, an increase in hydration repulsion of hydrated salt ions plays a major role in membrane fouling under high ionic strength conditions.
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http://dx.doi.org/10.1007/s11356-021-14170-4DOI Listing
May 2021

The clinical and radiologic outcomes of patients with different three-dimensional hemivertebra morphologies undergoing posterior-only hemivertebra resection and fusion.

World Neurosurg 2021 Apr 30. Epub 2021 Apr 30.

Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China.

Objective: To compare the clinical and radiologic outcomes of patients with different three-dimensional (3D) hemivertebra morphologies undergoing posterior-only hemivertebra resection and fusion.

Methods: Patients with congenital scoliosis (CS) due to single hemivertebra undergoing posterior-only hemivertebra resection and fusion from January 2010 to January 2018 were reviewed. After evaluating the 3D computed tomography (CT) images, CS patients were divided into a unison hemivertebra group and a discordant hemivertebra group. Clinical outcomes, radiological outcomes and incidence of complications were compared.

Results: A total of 42 consecutive patients with CS patients due to a single hemivertebra undergoing posterior-only hemivertebra resection and fusion were included in this study. The Cobb angle of the segmental curve was significantly improved postoperatively and at the last follow-up in both groups (all P<0.05). At both postoperation and the last follow-up, no significant differences were found in the incidence of complications, Cobb angle of the segmental curve, correction rate of the segmental curve, or other radiological outcomes between the unison hemivertebra group and discordant hemivertebra group (all P>0.05). Compared with the unison hemivertebra group, increased operation times (P=0.006) and intraoperative blood loss (P=0.037) were found in the discordant hemivertebra group.

Conclusions: For CS patients with unison hemivertebra or discordant hemivertebra, satisfactory radiological results were obtained by posterior-only hemivertebra resection and fusion. In terms of surgery, the radiological outcomes of discordant hemivertebra patients were similar to those of unison hemivertebra patients, but discordant hemivertebrae could easily result in longer operation times and more intraoperative blood loss.
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http://dx.doi.org/10.1016/j.wneu.2021.04.095DOI Listing
April 2021

Comparative Small RNA Profiling and Functional Exploration on Wheat With High- and Low-Cadmium Accumulation.

Front Genet 2021 15;12:635599. Epub 2021 Apr 15.

Anhui Province Key Laboratory of Farmland Ecological Conservation and Pollution Prevention, School of Resources and Environment, Anhui Agricultural University, Hefei, China.

Cadmium is a toxic metal widely found in workplaces and plant soil because of extensive industrialization. Wheat is an important source of food generated from plant soil. The different responses of wheat against different omic levels of cadmium have been observed and widely studied worldwide. With the development of high-throughput sequencing, micro-level biological research has extended to the microRNA level. In this study, high-cadmium-accumulating wheat cultivars (Annong9267) and low-cadmium-accumulating wheat cultivars (Qian 102032) were used as experimental models. The two cultivars were treated by Cd for 2 h to explore the microRNA profiles in root and leaf tissues through small RNA sequencing. Important small RNAs, such as tae-miR9663-5p and tae-miR6201, and potential small RNA-mediated mechanisms associated with cadmium accumulation were identified by summarizing specific microRNA profiling patterns and their respective target genes. At the wheat roots and leaves, differentially expressed small RNAs related to cadmium accumulation in different plant tissues (roots or leaves) were identified, and functional enrichment analyses on target genes of differentially expressed miRNAs in low- and high-cadmium-accumulating wheat cultivars in different plant tissues (roots or leaves) obtained some known mature miRNAs and new miRNAs. The identified miRNA will be regarded as a potential screening biomarker for low-cadmium-accumulating wheat.
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http://dx.doi.org/10.3389/fgene.2021.635599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084923PMC
April 2021

Improved Tolerance of Mycorrhizal Seedlings to Sulfuric Acid Rain Related to Phosphorus and Zinc Contents in Shoots.

J Fungi (Basel) 2021 Apr 14;7(4). Epub 2021 Apr 14.

State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Hangzhou 311300, China.

Acid rain (AR) is an increasingly serious environmental problem that frequently occurs in Southern China with sulfuric acid rain (SAR) as the main type. SAR can negatively affect the growth and physiological properties of trees, but mycorrhizal associations may mitigate such detrimental effects. However, the mechanisms by which arbuscular mycorrhizal fungi control SAR-induced impacts on plants remain unclear. A pot experiment was conducted on seedlings, an economically important tree species in Southern China, in which inoculated and non-inoculated seedlings were subjected to three simulated SAR regimes (pH of 5.6, 4.0, and 2.5, respectively) to examine the effects on the growth, osmotic regulation, and nutrient absorption of these seedlings. The results show that, although SAR had no effect on the accumulation of biomass, it significantly decreased the concentrations of proline and soluble protein, shoot Zn, P, K, and Ca concentrations, and the Fe and Mn concentrations of shoots and roots. Mycorrhizal inoculation, especially with , significantly increased total biomass, proline concentration, and the Zn, P, and K concentrations in the shoots of under lower pH conditions. Moreover, our findings suggest that the combination of root colonization, acid tolerance, and the concentrations of shoot-P, shoot-Zn, and root-Fe of jointly conferred mycorrhizal benefits on the plants under SAR conditions. Given the enhancement of the nutritional quality of owing to mycorrhizal associations, inoculation with may be preferable for the culturing and management of these plants under acidic conditions.
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http://dx.doi.org/10.3390/jof7040296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070988PMC
April 2021

Wearable and Implantable Electroceuticals for Therapeutic Electrostimulations.

Adv Sci (Weinh) 2021 04 19;8(8):2004023. Epub 2021 Feb 19.

Department of Material Science and Engineering University of Wisconsin-Madison Madison WI 53706 USA.

Wearable and implantable electroceuticals (WIEs) for therapeutic electrostimulation (ES) have become indispensable medical devices in modern healthcare. In addition to functionality, device miniaturization, conformability, biocompatibility, and/or biodegradability are the main engineering targets for the development and clinical translation of WIEs. Recent innovations are mainly focused on wearable/implantable power sources, advanced conformable electrodes, and efficient ES on targeted organs and tissues. Herein, nanogenerators as a hotspot wearable/implantable energy-harvesting technique suitable for powering WIEs are reviewed. Then, electrodes for comfortable attachment and efficient delivery of electrical signals to targeted tissue/organ are introduced and compared. A few promising application directions of ES are discussed, including heart stimulation, nerve modulation, skin regeneration, muscle activation, and assistance to other therapeutic modalities.
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http://dx.doi.org/10.1002/advs.202004023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061371PMC
April 2021

The PSMD14 inhibitor Thiolutin as a novel therapeutic approach for esophageal squamous cell carcinoma through facilitating SNAIL degradation.

Theranostics 2021 3;11(12):5847-5862. Epub 2021 Apr 3.

Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin 300060, China.

Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using and experiments. Immunoprecipitation and ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of and assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.
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http://dx.doi.org/10.7150/thno.46109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058732PMC
April 2021

Diagnostic Model Incorporating Clinicopathological Characteristics of Delphian Lymph Node Metastasis Risk Profiles in Papillary Thyroid Cancer.

Front Endocrinol (Lausanne) 2021 25;12:591015. Epub 2021 Mar 25.

Department of Maxillofacial & E.N.T. Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, China.

The Delphian lymph node (DLN), also known as the prelaryngeal node, is one component of the central lymph node. The DLN has been well studied in laryngeal cancer, although its significance in papillary thyroid cancer (PTC) remains unclear. We retrospectively analyzed 936 patients with PTC who underwent thyroidectomy by a single surgeon in Tianjin Cancer Hospital from 2017 to 2019. Moreover, 250 PTC patients who underwent thyroidectomy by another surgeon in Tianjin Cancer Hospital from January 2019 to April 2019 were used as a validation cohort. Among the 936 patients with PTC, 581 patients (62.1%) had DLNs, of which 177 samples with metastasis (177/581, 30.5%) were verified. DLN metastasis was significantly correlated with sex, age, tumor size, bilateral cancer, multifocality, extrathyroidal extension, lymphovascular invasion and central and lateral neck lymph node metastasis. Multivariate analysis revealed that independent risk factors for DLN metastasis included age, gender, tumor size, extrathyroid extension, lymphovascular invasion and central lymph node metastasis, which determined the nomogram. In particular, tumor size was proven to be one of the most predominant single predictors. The diagnostic model had an area under the curve (AUC) of 0.829 (95% confidence interval, 0.804-0.854). The internal and external validations of the nomogram were 0.819 and 0.745, respectively. Our results demonstrate that DLN metastasis appears to be a critical parameter for predicting metastatic disease of the central compartments. Furthermore, this study provides a precise criterion for assessing DLN metastasis and has great clinical significance for treating PTC.
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http://dx.doi.org/10.3389/fendo.2021.591015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027498PMC
March 2021

Oncologic Nomogram for Stage I Rectal Cancer to Assist Patient Selection for Adjuvant (Chemo)Radiotherapy Following Local Excision.

Front Oncol 2021 19;11:632085. Epub 2021 Mar 19.

Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China.

Because of the low rate of lymph node metastasis in stage I rectal cancer (RC), local resection (LR) can achieve high survival benefits and quality of life. However, the indications for postoperative adjuvant therapy (AT) remain controversial. A retrospective analysis was performed in 6,486 patients with RC (pT1/T2) using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were initially diagnosed from 2004 to 2016; following LR, 967 received AT and 5,519 did not. Propensity score matching (PSM) was used to balance the confounding factors of the two groups; the Kaplan-Meier method and the log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to screen independent prognostic factors and build a nomogram on this basis. X-tile software was used to divide the patients into low-, moderate-, and high-risk groups based on the nomogram risk score. Multivariate analysis found that age, sex, race, marital status, tumor size, T stage, and carcinoembryonic antigen (CEA) in the non-AT group were independent prognostic factors for stage I RC and were included in the nomogram prediction model. The C-index of the model was 0.726 (95% CI, 0.689-0.763). We divided the patients into three risk groups according to the nomogram prediction score and found that patients with low and moderate risks did not show an improved prognosis after AT. However, high-risk patients did benefit from AT. The nomogram of this study can effectively predict the prognosis of patients with stage I RC undergoing LR. Our results indicate that high-risk patients should receive AT after LR; AT is not recommended for low-risk patients.
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http://dx.doi.org/10.3389/fonc.2021.632085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017267PMC
March 2021

The complete chloroplast genome of (Adoxaceae).

Mitochondrial DNA B Resour 2021 Mar 22;6(3):997-998. Epub 2021 Mar 22.

China Construction Seventh Engineering Division Corp. Ltd, Zhengzhou, PR China.

 Thunb. is a large deciduous tree of Adoxaceae. In this study, the chloroplast genome sequence of is 158,392 bp, consisting of a large single-copy (LSC) region with 87,070 bp, a small single-copy (SSC) region with 18,242 bp , and two inverted repeat (IR) regions with 26,540 bp. The GC content in the chloroplast genome of is 38.1%. The chloroplast genome of contains 126 genes, including 83 protein-coding genes, 39 tRNA genes, and 4 rRNA genes. Phylogenetic tree showed that was clustered with .
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http://dx.doi.org/10.1080/23802359.2021.1891988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995874PMC
March 2021

Superhydrophobic-superoleophilic biochar-based foam for high-efficiency and repeatable oil-water separation.

Sci Total Environ 2021 Mar 17;780:146517. Epub 2021 Mar 17.

Tianjin Eco-City Environmental Protection Limited Company, Tianjin 300467, China.

Leakage accidents occurring during oil production and transportation are currently one of the most serious environmental problems worldwide. Developing efficient and environmentally friendly oil-water separation methods is the key to solve this problem. In this work, a facile method to fabricate a high-performance oil absorbent through the loading of ball-milled biochar (BMBC) and octadecylamine on the skeleton of melamine foam (MF) is reported. The resulting ball-milled biochar-based MF (BMBC@MF) displayed a complex three-dimensional porous structure. The BM biochar on the surface of BMBC@MF forms nano/μm-scale folds, which reduced the surface energy of BMBC@MF after grafted octadecylamine. These structures resulted in the conversion of the hydrophilic surface of MF to hydrophobic surface. These characteristics made the modified foam an excellent oil absorbent with a high oil absorption capacity (43-155 times its own weight) and extraordinary recyclability. Furthermore, the BMBC@MF could maintain high hydrophobicity and adsorption stability in a wide pH range (from 1 to 11). More importantly, BM biochar is a cheap and readily available material to make BMBC@MF possible for large-scale production. Therefore, this work provides an effective way for low-cost, environmentally friendly, and large-scale production of superhydrophobic adsorbents for oil-water separation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146517DOI Listing
March 2021

ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum.

Front Genet 2021 4;12:616329. Epub 2021 Mar 4.

Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Hemifacial microsomia (HM) is a craniofacial congenital defect involving the first and second branchial arch, mainly characterized by ocular, ear, maxilla-zygoma complex, mandible, and facial nerve malformation. HM follows autosomal dominant inheritance. Whole-exome sequencing of a family revealed a missense mutation in a highly conserved domain of . ITPR1 is a calcium ion channel. By studying 's expression pattern, we found that ITPR1 participated in craniofacial development, especially the organs that corresponded to the phenotype of HM. In zebrafish, , which is homologous to human , is closely related to craniofacial bone formation. The knocking down of in zebrafish could lead to a remarkable decrease in craniofacial skeleton formation. qRT-PCR suggested that knockdown of could increase the expression of while decreasing the mRNA level of Dlx5/6. Our findings highlighted ITPR1's role in craniofacial formation for the first time and suggested that mutation contributes to human HM.
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http://dx.doi.org/10.3389/fgene.2021.616329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971309PMC
March 2021

Borehole wall tensile caving instability in the horizontal well of deep brittle shale.

Sci Prog 2021 Jan-Mar;104(1):368504211002330

State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, China.

Introduction: With the increasing drilling depth of shale formation, downhole collapse is a frequent occurrence, which often manifests as borehole wall caving.

Methods: We used the deep shale of the Longmaxi Formation to conduct the mechanical loading and unloading experiments under different downhole working conditions and a theoretical evaluation method of borehole wall caving and instability was proposed.

Results And Discussion: As the confining pressure and axial load increased, the acoustic velocity increased. When a certain value was reached, the acoustic velocity of the rock mass had minimal changes. As the confining pressure continued to unload and decrease, the acoustic velocity decreased. At the moment of core failure, the acoustic velocity suddenly dropped. When the axial force of loading was constant, the unloading speed of confining pressure increased, and shale could easily be destroyed. The pressure at the well bottom changed rapidly, the likelihood of borehole wall failure increased.

Conclusion: The deep shale has high brittleness. Under the bottom-hole pressure, the borehole wall rock was prone to brittle fracture failure along the parallel bedding surface. Under different working conditions, obvious changes could be observed in the pressure of the effective fluid column at the well bottom. The pressure changed rapidly, which, in turn, caused the rock at the well bottom to break down, thereby resulting in borehole wall caving. After tripping out and turning the pump off, the shale tensile stress in the upper and lower sidewalls of the horizontal well section was responsible for tensile caving.
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http://dx.doi.org/10.1177/00368504211002330DOI Listing
March 2021

Expression and Purification of Yeast-derived GPCR, Gα and Gβγ Subunits for Structural and Dynamic Studies.

Bio Protoc 2021 Feb 20;11(4):e3919. Epub 2021 Feb 20.

Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA.

In the last several years, as evidence of a surged number of GPCR-G complex structures, the expressions of GPCRs and G proteins for structural biology have achieved tremendous successes, mostly in insect and mammalian cell systems, resulting in more than 370 structures of over 70 GPCRs have been resolved. However, the challenge remains, particularly in the conformational transition and dynamics study area where a much higher quantity of the receptors and G proteins is required even in comparison to X-ray and cryo-EM (5 mg/ml, 3 μl/sample) when NMR spectroscopy (5 mg/ml, 250 μl /sample) is applied. As a result, the expression levels of the insect and mammalian systems are also difficult to meet this demand, not to mention the prohibitive cost of producing GPCRs and G proteins using these systems for a vast majority of laboratories. Therefore, exploration of an effective, affordable, and practical approach with broad applicability is demanded. expression system has shown its promise in the GPCR preparation with many merits that other eukaryotic expression systems can't compete with. GPCRs expressed in this system are inexpensive, easy-to-manipulate, and capable of isotopically labeling. Herein, we present related protocols recently developed and upgraded in our lab, including expressions and purifications of derived GPCR along with Gα and Gβγ proteins. We anticipate that these protocols will advance the conformational transition and dynamics studies of the GPCR and its complexes.
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http://dx.doi.org/10.21769/BioProtoc.3919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952927PMC
February 2021

Bioresorbable Primary Battery Anodes Built on Core-Double-Shell Zinc Microparticle Networks.

ACS Appl Mater Interfaces 2021 Mar 17;13(12):14275-14282. Epub 2021 Mar 17.

Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

Bioresorbable implantable electronics require power sources that are also bioresorbable with controllable electrical output and lifetime. In this paper, we report a bioresorbable zinc primary battery anode filament based on a zinc microparticle (MP) network coated with chitosan and AlO double shells. When discharged in 0.9% NaCl saline, a Zn MP filament with a 0.17 × 2 mm cross-sectional area exhibited a stable voltage output of 0.55 V at a current of 0.01 mA. Covered by chitosan and AlO double shells, the zinc MP filament exhibited a directional dissolution behavior with a tunable lifetime approximately linear to its length. A stable 200 h discharging time was achieved with a 15 mm Zn MP filament. The maximum output power was found to be 12 μW at 0.03 mA for one filament. The linearity relationship between the current output and the filament cross-sectional area suggested a facile strategy to raise the power output at constant discharging voltage. The filaments could also be connected in series and in parallel to boost its overall voltage and current output, demonstrating their excellent integration capability. This work presents a promising pathway toward bioresorbable transient batteries with controllable lifetime and power output, demonstrating a great potential for powering transient implantable biomedical devices.
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http://dx.doi.org/10.1021/acsami.1c00602DOI Listing
March 2021

Thickness-Dependent Piezoelectric Property from Quasi-Two-Dimensional Zinc Oxide Nanosheets with Unit Cell Resolution.

Research (Wash D C) 2021 25;2021:1519340. Epub 2021 Feb 25.

Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

A quantitative understanding of the nanoscale piezoelectric property will unlock many application potentials of the electromechanical coupling phenomenon under quantum confinement. In this work, we present an atomic force microscopy- (AFM-) based approach to the quantification of the nanometer-scale piezoelectric property from single-crystalline zinc oxide nanosheets (NSs) with thicknesses ranging from 1 to 4 nm. By identifying the appropriate driving potential, we minimized the influences from electrostatic interactions and tip-sample coupling, and extrapolated the thickness-dependent piezoelectric coefficient (). By averaging the measured from NSs with the same number of unit cells in thickness, an intriguing tri-unit-cell relationship was observed. From NSs with 3 unit cell thickness ( = 1, 2, 3), a bulk-like at a value of ~9 pm/V was obtained, whereas NSs with other thickness showed a ~30% higher of ~12 pm/V. Quantification of as a function of ZnO unit cell numbers offers a new experimental discovery toward nanoscale piezoelectricity from nonlayered materials that are piezoelectric in bulk.
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http://dx.doi.org/10.34133/2021/1519340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936626PMC
February 2021

Ligand modulation of the conformational dynamics of the A adenosine receptor revealed by single-molecule fluorescence.

Sci Rep 2021 Mar 15;11(1):5910. Epub 2021 Mar 15.

Department of Physics, University of Toronto, Toronto, ON, M5S 1A7, Canada.

G protein-coupled receptors (GPCRs) are the largest class of transmembrane proteins, making them an important target for therapeutics. Activation of these receptors is modulated by orthosteric ligands, which stabilize one or several states within a complex conformational ensemble. The intra- and inter-state dynamics, however, is not well documented. Here, we used single-molecule fluorescence to measure ligand-modulated conformational dynamics of the adenosine A receptor (AR) on nanosecond to millisecond timescales. Experiments were performed on detergent-purified AR in either the ligand-free (apo) state, or when bound to an inverse, partial or full agonist ligand. Single-molecule Förster resonance energy transfer (smFRET) was performed on detergent-solubilized AR to resolve active and inactive states via the separation between transmembrane (TM) helices 4 and 6. The ligand-dependent changes of the smFRET distributions are consistent with conformational selection and with inter-state exchange lifetimes ≥ 3 ms. Local conformational dynamics around residue 229 on TM6 was measured using fluorescence correlation spectroscopy (FCS), which captures dynamic quenching due to photoinduced electron transfer (PET) between a covalently-attached dye and proximal aromatic residues. Global analysis of PET-FCS data revealed fast (150-350 ns), intermediate (50-60 μs) and slow (200-300 μs) conformational dynamics in AR, with lifetimes and amplitudes modulated by ligands and a G-protein mimetic (mini-G). Most notably, the agonist binding and the coupling to mini-G accelerates and increases the relative contribution of the sub-microsecond phase. Molecular dynamics simulations identified three tyrosine residues (Y112, Y288, and Y290) as being responsible for the dynamic quenching observed by PET-FCS and revealed associated helical motions around residue 229 on TM6. This study provides a quantitative description of conformational dynamics in AR and supports the idea that ligands bias not only GPCR conformations but also the dynamics within and between distinct conformational states of the receptor.
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http://dx.doi.org/10.1038/s41598-021-84069-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960716PMC
March 2021

The Preventive and Control Recommendations on Patient With Cleft Lip and Palate During COVID-19 Pandemic in Shanghai.

J Craniofac Surg 2021 Mar-Apr 01;32(2):e223-e226

Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Oral Diseases Clinical Research Center, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, People's Republic of China.

Abstract: As Corona Virus Disease 2019 (COVID-19) has been gradually controlled domestically, various industries began to resume production in an orderly way. Attention should be paid to the disease and population characteristics of patients with cleft lip with/without palate during diagnosis and treatment. This article summarized and provided prevention and control recommendations on management strategies during hospitalization and protective measures of patients and healthcare workers, hoping to minimize the spread of disease and create a relatively safe environment for medical work.
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http://dx.doi.org/10.1097/SCS.0000000000007067DOI Listing
March 2021

Speech Outcomes Comparison Between Adult Velopharyngeal Insufficiency and Patients With Unrepaired Cleft Palate.

J Craniofac Surg 2021 Mar-Apr 01;32(2):655-659

Department of Oral and Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research, Institute of Stomatology, Shanghai, China.

Objective: This study compared the speech outcomes of adult velopharyngeal insufficiency patients and adult cleft palate (ACP) patients, and explored whether there was any difference in the phonological level of these 2 types of patients.

Methods: Perceptual evaluation was used to assess speech intelligibility, hypernasality and compensatory articulation in 89 adult patients with velopharyngeal insufficiency and 35 adult patients with unrepaired cleft palate. Each group was divided into complete cleft palate and incomplete cleft palate (including submucous cleft palate). The phonological differences were compared between the 2 groups of patients and 2 types of cleft palate.

Results: The mean speech intelligibility was 43.04% in velopharyngeal insufficiency group and 32.87% in ACP group. There was a significant difference in speech intelligibility between the 2 groups by T test, t = 2.916 (P < 0.01), speech intelligibility between 2 types of cleft palate was no significant difference. Also, there was a significant difference between the 2 groups in the constitution of hypernasality degree by Chi-Square test, x2 = 31.650 (P < 0.01), compensatory articulation were present in 74.3% ACP patients (26/35) and 47.2% velopharyngeal insufficiency patients (42/89), x2 = 7.446 (P < 0.01), there was a significant difference in incidence of compensatory articulation between the 2 groups.

Conclusions: Adult patients with unpaired cleft palate present an even worse speech intelligibility and hypernasality degree than velopharyngeal insufficiency patients after cleft palate repair, regardless of the cleft type. Additionally, patients in ACP group have a higher incidence of compensatory articulation than that in incomplete cleft palate group. In sequenced treatments of cleft lip and palate, evaluation and treatment of speech disorders cannot be ignored.
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http://dx.doi.org/10.1097/SCS.0000000000006994DOI Listing
March 2021

Heat-killed Lactobacillus acidophilus mediates Fusobacterium nucleatum induced pro-inflammatory responses in epithelial cells.

FEMS Microbiol Lett 2021 Apr;368(5)

Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.

Probiotics is widespreadly used nowadays. However, the safety issue with the use of live probiotics is still a matter of contention. In recent years, an expanding body of evidence supports the beneficial role of heat-killed probiotics in the maintenance of systemic health, whereas the role of these heat-killed bacteria on periodontal health remains unclear. This study aimed to evaluate the effects of heat-killed probiotics on periodontal pathogen virulence and associated mechanisms. We demonstrated that heat-killed Lactobacillus acidophilus was able to coaggregate with Fusobacterium nucleatum, the bridging bacteria of oral biofilm, and inhibit the adhesion and invasion of F. nucleatum, leading to a subsequent elimination of pro-inflammatory cytokine production in oral epithelial cells. This coaggregation further caused a suppression of the virulence gene fap2 expression in F. nucleatum. Therefore, heat-killed L. acidophilus might downregulate the pro-inflammatory cytokine expression in epithelial cells via coaggregation with F. nucleatum and suppression of F. nucleatum fap2 expression, which was the first demonstration that heat-killed probiotics modulate periodontal disease pathogenesis via coaggregation. Collectively, this finding provides new evidence that heat-killed probiotics might exert beneficial effects to periodontal health by coaggregating with periodontal pathogens and modulating their virulence.
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http://dx.doi.org/10.1093/femsle/fnaa160DOI Listing
April 2021

Multifunctional Artificial Artery from Direct 3D Printing with Built-In Ferroelectricity and Tissue-Matching Modulus for Real-Time Sensing and Occlusion Monitoring.

Adv Funct Mater 2020 Sep 21;30(39). Epub 2020 Jul 21.

Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.

Treating vascular grafts failure requires complex surgery procedures and is associated with high risks. A real-time monitoring vascular system enables quick and reliable identification of complications and initiates safer treatments early. Here, an electric fieldassisted 3D printing technology is developed to fabricate in situ-poled ferroelectric artificial arteries that offer battery-free real-time blood pressure sensing and occlusion monitoring capability. The functional artery architecture is made possible by the development of a ferroelectric biocomposite which can be quickly polarized during printing and reshaped into devised objects. The synergistic effect from the potassium sodium niobite particles and the polyvinylidene fluoride polymer matrix yields a superb piezoelectric performance (bulk-scale > 12 pC N). The sinusoidal architecture brings the mechanical modulus close to the level of blood vessels. The desired piezoelectric and mechanical properties of the artificial artery provide an excellent sensitivity to pressure change (0.306 mV mmHg, > 0.99) within the range of human blood pressure (11.25-225.00 mmHg). The high pressure sensitivity and the ability to detect subtle vessel motion pattern change enable early detection of partial occlusion (e.g., thrombosis), allowing for preventing grafts failure. This work demonstrates a promising strategy of incorporating multifunctionality to artificial biological systems for smart healthcare systems.
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http://dx.doi.org/10.1002/adfm.202002868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928534PMC
September 2020

A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome.

BMC Med Genomics 2021 Mar 2;14(1):68. Epub 2021 Mar 2.

United Diagnostic and Research Center for Clinical Genetics, Women and Children's Hospital, School of Medicine and School of Public Health, Xiamen University, Xiamen, 361102, Fujian, China.

Background: KBG syndrome is a rare autosomal dominant genetic disease mainly caused by pathogenic variants of ankyrin repeat domain-containing protein 11 (ANKRD11) or deletions involving ANKRD11. Herein, we report a novel de novo heterozygous frameshift ANKRD11 variant via whole exome sequencing in a Chinese girl with KBG syndrome.

Case Presentation: A 2-year-2-month-old girl presented with a short stature and developmental delay. Comprehensive physical examinations, endocrine laboratory tests and imaging examination were performed. Whole-exome sequencing and Sanger sequencing were used to detect and confirm the variant associated with KBG in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools. The patient was diagnosed as KBG syndrome with a short stature and developmental delay, as well as characteristic craniofacial abnormalities, including a triangular face, long philtrum, wide eyebrows, a broad nasal bridge, prominent and protruding ears, macrodontia of the upper central incisors, dental crowding, and binocular refractive error. Her skeletal anomalies included brachydactyly, fifth finger clinodactyly, and left-skewed caudal vertebrae. Electroencephalographic results generally showed normal background activity with sporadic spikes and slow wave complexes, as well as multiple spikes and slow wave complexes in the bilateral parietal, occipital, and posterior temporal regions during non-rapid-eye-movement sleep. Brain MRI showed a distended change in the bilateral ventricles and third ventricle, as well as malformation of the sixth ventricle. Whole exome sequencing revealed a novel heterozygous frameshift variant in the patient, ANKRD11 c.1366_1367dup, which was predicted to be pathogenic through in silico analysis. The patient had received physical therapy since 4 months of age, and improvement of gross motor dysfunction was evident.

Conclusions: The results of this study expand the spectrum of ANKRD11 variants in KBG patients and provide clinical phenotypic data for KBG syndrome at an early age. Our study also demonstrates that whole exome sequencing is an effective method for the diagnosis of rare genetic disorders.
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http://dx.doi.org/10.1186/s12920-021-00920-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927266PMC
March 2021

Dental Implants Loaded With Bioactive Agents Promote Osseointegration in Osteoporosis: A Review.

Front Bioeng Biotechnol 2021 9;9:591796. Epub 2021 Feb 9.

School of Stomatology, Xuzhou Medical University, Xuzhou, China.

Implant-supported dentures are widely used in patients with defect or loss of dentition because these have higher chewing efficiency and do not damage the adjacent teeth compared with fixed or removable denture. An implant-supported denture carries the risk of failure in some systemic diseases, including osteoporosis, because of a non-ideal local microenvironment. Clinically common physical and chemical modifications are used to change the roughness of the implant surface to promote osseointegration, but they have limitations in promoting osteoinduction and inhibiting bone resorption. Recently, many researchers have focused on the study of bioactive modification of implants and have achieved promising results. Herein we have summarized the progress in bioactive modification strategy to promote osseointegration by regulating the local osteoporotic microenvironment.
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http://dx.doi.org/10.3389/fbioe.2021.591796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903335PMC
February 2021

A network pharmacology approach: Inhibition of the NF-κB signaling pathway contributes to the NASH preventative effect of an Oroxylum indicum seed extract in oleic acid-stimulated HepG2 cells and high-fat diet-fed rats.

Phytomedicine 2021 Feb 12:153498. Epub 2021 Feb 12.

College of Life Science, Yangtze University, Jingzhou, Hubei 434000, China. Electronic address:

Background: The incidence of nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has significantly increased in recent years and has become an important public health issue. However, no U.S. Food and Drug Administration (FDA)-approved first-line drug is currently available for the treatment of NAFLD and NASH; therefore, research on new drugs is currently a hot topic. Oroxylum indicum (Linn.) Kurz is extensively distributed in South China and South Asia and has many biological activities. However, its effects on NAFLD or even NASH and the corresponding mechanisms are still not clear.

Purpose: To investigate the effect and mechanism of O. indicum seed extract (OISE) on preventing anti-inflammatory action in the progression from simple nonalcoholic fatty liver (NAFL) to NASH.

Methods: A network pharmacology method to construct ingredient-target networks and the protein-protein interaction (PPI) network of OISE in NASH were constructed for topological analyses and hub-target screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Simultaneously, in vitro and in vivo experiments investigated the effect and mechanism of OISE, baicalein, and chrysin on inflammation by biochemical indicator detection, luciferase reporters, pathological staining, and immunoblotting in oleic acid-stimulated HepG2 cells or in high-fat diet-fed rats.

Results: The network pharmacology showed that OISE prevented the development and progression of NAFL into NASH through various pathways and targets and that the nuclear factor NF-κB (NF-κB) pathway regulated by baicalein and chrysin played an important role in the treatment of NASH. In in vitro experiments, we further showed that OISE and its ingredients, namely, baicalein and chrysin, all improved the inflammatory status in oleic acid-stimulated HepG2 cells, inhibited the nuclear transcriptional activities of NF-κB, increased the IκB level, and decreased the phosphorylation level of NF-κB. Furthermore, in a high-fat diet-induced NASH model in rats, we also showed that OISE prevented the development and progression of NASH by inhibiting the nuclear transcriptional activity of NF-κB.

Conclusion: OISE suppressed inflammatory responses and prevented the development and progression of NAFL into NASH through inhibition of the nuclear transcriptional activity of NF-κB. OISE may be used to treat NAFLD through many functions, including an increase in insulin sensitivity, a decrease in lipid accumulation in the liver, suppression of inflammation, and clearance of free radicals.
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http://dx.doi.org/10.1016/j.phymed.2021.153498DOI Listing
February 2021

Paeoniflorin attenuates DHEA-induced polycystic ovary syndrome via inactivation of TGF-β1/Smads signaling pathway .

Aging (Albany NY) 2021 02 26;13(5):7084-7095. Epub 2021 Feb 26.

Department of Pharmacy, The First People's Hospital of Nantong, Nan Tong 226001, Jiangsu, PR China.

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrine disorders which are involved in complicated and unknown pathogenic mechanisms. Paeoniflorin (PAE) plays a significant anti-fibrotic role according to previous studies. The aim of the present study was to investigate the effect of PAE on ovarian fibrosis and its underlying mechanism in PCOS development. An animal model of PCOS was established by subcutaneous injection of 60mg/kg/d dehydroepiandrosterone (DHEA) for 35 consecutive days. Rats in PAE-L, PAE-M and PAE-H groups were administrated by gavage with PAE (20, 40, 80 mg/kg/d) for 4 weeks. Our results indicated that DHEA-induced PCOS rats showed similar phenotypes with PCOS patients. PAE could significantly block the DHEA-induced decline of ovary weight and organ coefficient, shorten the prolonged diestrus period, and regulate the irregular estrous cycle of PCOS rats. Moreover, PAE regulated reproductive hormone levels and improved ovarian fibrosis induced by DHEA. PAE treatment could also reduce the expression levels of TGF-β1 and Smad3, and increase the expression levels of Smad7 and MMP2. In conclusion, PAE significantly attenuated the ovarian fibrosis in PCOS, which could be mediated by TGF-β1/Smads signaling pathway. Herein, PAE can be used for the treatment of ovarian fibrosis in PCOS progression.
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http://dx.doi.org/10.18632/aging.202564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993663PMC
February 2021

Predictive value of the Delphian lymph node in cervical lymph node metastasis of papillary thyroid carcinoma.

Eur J Surg Oncol 2021 Feb 18. Epub 2021 Feb 18.

The Department of Maxillofacial and Otorhinolaryngology Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, 300060, China. Electronic address:

Introduction: Delphian lymph node metastasis (DLNM) has proven to be a risk factor for a poor prognosis in head and neck malignancies. This study aimed to reveal the clinical features and evaluate the predictive value of the Delphian lymph node (DLN) in papillary thyroid carcinoma (PTC) to guide the extent of surgery.

Methods: Tianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 2017 to 2020, and 516 PTC patients with DLN detection were enrolled. Retrospective analysis was performed, while multivariate analysis was performed to identify the risk factors for DLNM.

Results: Among the 516 PTC patients with DLN detection, the DLN metastasis rate was 25.39% (131/516). Tumor size >1 cm, location in the upper 1/3, central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM) and lymphovascular invasion were independent risk factors for DLNM. Patients with DLNM had a higher incidence of ipsilateral CLNM, contralateral CLNM (CCLNM) and LLNM, and larger numbers and size of metastatic CLNs than those without DLNM. The incidence of CLNM among cN0 patients with DLNM was higher than that among those without DLNM. The incidence of CCLNM among unilateral cN + patients with DLNM was similarly higher than that among patients without DLNM.

Conclusions: DLNM indicates a high likelihood and large number of cervical lymph nodes metastases in PTC patients. Surgeons are strongly recommended to detect DLN status during operation by means of frozen pathology, so as to evaluate the possibility of cervical nodal metastasis and decide the appropriate extent of surgery.
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http://dx.doi.org/10.1016/j.ejso.2021.02.010DOI Listing
February 2021

Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges miR-3653-3p.

Stem Cell Res Ther 2021 Feb 25;12(1):150. Epub 2021 Feb 25.

Department of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, #107 West Yan Jiang Road, Guangzhou, Guangdong, 510120, China.

Background: Little is known about the implications of circRNAs in the effects of melatonin (MEL) on bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoporosis (OP) progression. The aim of our study was to investigate circRNAs in MEL-regulated BMSC differentiation and OP progression.

Methods: BMSC osteogenic differentiation was measured by qRT-PCR, western blot (WB), Alizarin Red, and alkaline phosphatase (ALP) staining. Differential circRNA and mRNA profiles of BMSCs treated by MEL were characterized by deep sequencing, followed by validation using RT-PCR, Sanger sequencing, and qRT-PCR. Silencing and overexpression of circ_0003865 were conducted for functional investigations. The sponged microRNAs and targeted mRNAs were predicted by bioinformatics and validated by qRT-PCR, RNA pull-down, and dual-luciferase reporter assay. The function of miR-3653-3p and circ_0003865/miR-3653-3p/growth arrest-specific gene 1 (GAS1) cascade was validated for the osteogenic differentiation of BMSCs by CCK-8, qRT-PCR, WB, Alizarin Red, and ALP staining. The effects of circ_0003865 on OP development were tested in murine OP model.

Results: MEL promoted osteogenic differentiation of BMSCs. RNA sequencing revealed significant alterations in circRNA and mRNA profiles associated with multiple biological processes and signaling pathways. Circ_0003865 expression in BMSCs was significantly decreased by MEL treatment. Silencing of circ_0003865 had no effect on proliferation while promoted osteogenic differentiation of BMSCs. Overexpression of circ_0003865 abrogated the promotion of BMSC osteogenic differentiation induced by MEL, but proliferation of BMSCs induced by MEL had no change whether circ_0003865 was overexpression or not. Furthermore, circ_0003865 sponged miR-3653-3p to promote GAS1 expression in BMSCs. BMSC osteogenic differentiation was enhanced by miR-3653-3p overexpression while BMSC proliferation was not affected. By contrast, miR-3653-3p silencing mitigated the promoted BMSC osteogenic differentiation caused by circ_0003865 silencing, but had no effect on proliferation. Finally, circ_0003865 silencing repressed OP development in mouse model.

Conclusion: MEL promotes BMSC osteogenic differentiation and inhibits OP pathogenesis by suppressing the expression of circ_0003865, which regulates GAS1 gene expression via sponging miR-3653-3p.
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http://dx.doi.org/10.1186/s13287-021-02224-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908669PMC
February 2021

The complete chloroplast genome of (Ulmaceae).

Mitochondrial DNA B Resour 2021 Feb 11;6(2):517-518. Epub 2021 Feb 11.

China Construction Seventh Engineering Division Corp. Ltd., Zhengzhou, China.

C.K. Schneid. is a large deciduous tree of Ulmaceae. In this study, the chloroplast genome sequence of was 159,064 bp in length, consisting of a large single-copy (LSC) region with 86,139 bp, a small single-copy (SSC) region with 19,137 bp, and two inverted repeat regions (IRs) with 26,894 bp. The GC content in the chloroplast genome of was 36.3%. The chloroplast genome of contained 127 genes, including 86 protein-coding genes, 37 tRNA genes, and four rRNA genes. Phylogenetic tree showed that was clustered with .
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http://dx.doi.org/10.1080/23802359.2021.1872445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889233PMC
February 2021

PAK4 suppresses motor neuron degeneration in hSOD1 -linked amyotrophic lateral sclerosis cell and rat models.

Cell Prolif 2021 Apr 21;54(4):e13003. Epub 2021 Feb 21.

Department of Neurology, The First Clinical College of Harbin Medical University, Harbin, China.

Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons (MN). CREB pathway-mediated inhibition of apoptosis contributes to neuron protection, and PAK4 activates CREB signalling in diverse cell types. This study aimed to investigate PAK4's effect and mechanism of action in ALS.

Methods: We analysed RNA levels by qRT-PCR, protein levels by immunofluorescence and Western blotting, and apoptosis by flow cytometry and TUNEL staining. Cell transfection was performed for in vitro experiment. Mice were injected intraspinally to evaluate PAK4 function in vivo experiment. Rotarod test was performed to measure motor function.

Results: The expression and activation of PAK4 significantly decreased in the cell and mouse models of ALS as the disease progressed, which was caused by the negative regulation of miR-9-5p. Silencing of PAK4 increased the apoptosis of MN by inhibiting CREB-mediated neuroprotection, whereas overexpression of PAK4 protected MN from hSOD1 -induced degeneration by activating CREB signalling. The neuroprotective effect of PAK4 was markedly inhibited by CREB inhibitor. In ALS models, the PAK4/CREB pathway was inhibited, and cell apoptosis increased. In vivo experiments revealed that PAK4 overexpression in the spinal neurons of hSOD1 mice suppressed MN degeneration, prolonged survival and promoted the CREB pathway.

Conclusions: PAK4 protects MN from degeneration by activating the anti-apoptotic effects of CREB signalling, suggesting it may be a therapeutic target in ALS.
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http://dx.doi.org/10.1111/cpr.13003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016643PMC
April 2021