Publications by authors named "Gang Zhang"

706 Publications

Novel core-shell nanocomposite as an effective heterogeneous catalyst for the synthesis of benzimidazoles.

Nanotechnology 2021 Apr 12;32(26):265603. Epub 2021 Apr 12.

College of Science, Northeastern University, Shengyang 110819, People's Republic of China.

Core-shell nanocomposites with a catalytic metal-organic framework (MOF) shell are more effective and stable than bare MOF. We have successfully designed an effective heterogeneous catalyst for the synthesis of benzimidazole by integrating acidic catalytic activity, and promoted the aerobic oxidation and magnetic recyclability of core-shell nanocomposite FeO@SiO@UiO-66. The FeO@SiO core is encapsulated by the in situ-grown UiO-66 shell, and the UiO-66 shell retains the porous structure and crystallinity of UiO-66 with abundant exposed Lewis acid sites. It shows high catalytic ability for the synthesis of various benzimidazoles through the acid-catalyzed condensation and aerobic oxidation with in situ oxygen. The FeO@SiO core provides magnetic recyclability of FeO@SiO@UiO-66, and maintains high catalytic ability and stability over six cycles.
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http://dx.doi.org/10.1088/1361-6528/abef2fDOI Listing
April 2021

Emerging mechanisms of valproic acid-induced neurotoxic events in autism and its implications for pharmacological treatment.

Biomed Pharmacother 2021 May 16;137:111322. Epub 2021 Feb 16.

Key Lab of Cardiovascular and Cerebrovascular Medicine, Drug Target and Drug Discovery Center, School of Pharmacy, Nanjing Medical University, Nanjing, China; Institute of Brain Sciences, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Autism spectrum disorder (ASD) is a sort of mental disorder marked by deficits in cognitive and communication abilities. To date no effective cure for this pernicious disease has been available. Valproic acid (VPA) is a broad-spectrum, antiepileptic drug, and it is also a potent teratogen. Epidemiological studies have shown that children exposed to VPA are at higher risk for ASD during the first trimester of their gestational development. Several animal and human studies have demonstrated important behavioral impairments and morphological changes in the brain following VPA treatment. However, the mechanism of VPA exposure-induced ASD remains unclear. Several factors are involved in the pathological phase of ASD, including aberrant excitation/inhibition of synaptic transmission, neuroinflammation, diminished neurogenesis, oxidative stress, etc. In this review, we aim to outline the current knowledge of the critical pathophysiological mechanisms underlying VPA exposure-induced ASD. This review will give insight toward understanding the complex nature of VPA-induced neuronal toxicity and exploring a new path toward the development of novel pharmacological treatment against ASD.
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http://dx.doi.org/10.1016/j.biopha.2021.111322DOI Listing
May 2021

Decitabine inhibits the proliferation of human T-cell acute lymphoblastic leukemia molt4 cells and promotes apoptosis partly by regulating the PI3K/AKT/mTOR pathway.

Oncol Lett 2021 May 2;21(5):340. Epub 2021 Mar 2.

Department of Hematology, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China.

T cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematological cancer; however, there is a lack of effective chemotherapeutic or targeted drugs for the treatment of T-ALL. Decitabine is a DNA demethylation agent but it has not been used for T-ALL treatment. Therefore, the present study aimed to assess the inhibitory effect of decitabine on T-ALL molt4 cells and determine its regulatory role in the PI3K/AKT/mTOR pathway. Molt4 cells were stimulated with decitabine , after which cell proliferation, apoptosis and cell cycle analyses were performed to assess cell viability. Subcellular morphology was observed using transmission electron microscopy. Expression levels of phosphate and tension homology (PTEN), genes involved in the PI3K/AKT/mTOR pathway and the corresponding downstream genes were analyzed using reverse transcription-quantitative PCR and western blotting. The results showed that decitabine induced apoptosis, inhibited proliferation and arrested molt4 cells in the G phase. Following decitabine intervention, an increase in the number of lipid droplets, autophagosomes and mitochondrial damage was observed. At concentrations of 1 and 10 µM, decitabine downregulated the expression of PI3K, AKT, mTOR, P70S6 and eukaryotic initiating factor 4E-binding protein 1, which in turn upregulated PTEN expression; however, 50 µM decitabine downregulated PTEN levels. Overall, these results demonstrated that decitabine reduced the viability of molt4 cells partly by inhibiting the PI3K/AKT/mTOR pathway via PTEN, especially at low decitabine concentrations.
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http://dx.doi.org/10.3892/ol.2021.12601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967925PMC
May 2021

Novel core-shell nanocomposite as an effective heterogeneous catalyst for synthesis of benzimidazoles.

Nanotechnology 2021 Mar 16. Epub 2021 Mar 16.

Jiangxi Key Laboratory of Surface Engineering, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, CHINA.

The core-shell nanocomposite with catalytic metal-organic framework (MOF) shell is more effective and stable than bare MOF. We have successfully designed an effective heterogeneous catalyst for the synthesis of benzimidazole by integrating acidic catalytic activity, promoted aerobic oxidation and magnetic recyclability into core-shell nanocomposite Fe3O4@SiO2@UiO-66. Fe3O4@SiO2 core is encapsulated by the in-situ growing UiO-66 shell, and the UiO-66 shell retains the porous structure and crystallinity of UiO-66 with abundant exposed Lewis acid sites, which shows high catalytic ability for the synthesis of various benzimidazole through the acid-catalyzed condensation and aerobic oxidation with in-situ oxygen. The Fe3O4@SiO2 core provides magnetic recyclability of Fe3O4@SiO2@UiO-66, which maintains high catalytic ability and stability for 6 cycles.
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http://dx.doi.org/10.1088/1361-6528/abef2fDOI Listing
March 2021

Simultaneous measurement of refractive index and temperature or temperature and axial strain based on an inline Mach-Zehnder interferometer with TCF-TF-TCF structure.

Appl Opt 2021 Feb;60(6):1522-1528

A refractive index (RI) and temperature or a temperature and axial strain sensor based on an inline Mach-Zehnder interferometer with thin core fiber (TCF)-thin fiber (TF)-TCF structure is proposed and experimentally demonstrated, requiring only the cleaving and fusion splicing methods. The operation principle depends on the effect that the TF cladding modes interfere with the core mode as an optical coupler. The RI, temperature, or axial strain variations can lead to resonance dip variations in the interferometer spectra, and the RI, temperature, or axial strain sensitivity can be measured by monitoring the wavelength shifts of resonance dips. Then we can measure both RI and temperature, or temperature and axial strain through the demodulation matrix. Four sensors with different TF lengths are fabricated based on numerical simulation. A 15 mm long TF sensor displays an RI sensitivity as high as -174.357/, temperature sensitivities in the glycerin solution and the air of 12.47 and 26.19 pm/°C, and axial strain sensitivity of -3.43×10/µ. Moreover, due to its simple manufacture, high cost-effectiveness and compactness, the proposed sensor has a broad application prospect in physical, chemical, and biological sensing.
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http://dx.doi.org/10.1364/AO.417124DOI Listing
February 2021

Open-Structured Nanotubes with Three-Dimensional Ion-Accessible Pathways for Enhanced Li Conductivity in Composite Solid Electrolytes.

ACS Appl Mater Interfaces 2021 Mar 9;13(11):13183-13190. Epub 2021 Mar 9.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, Hubei, P. R. China.

Composite solid electrolytes (CSEs) hold great promise toward safe lithium metal batteries with high energy density, due to integration of the merits of polymer matrixes and fillers. Rational design of filler nanostructures has attracted increasing attention for improving the ionic transport of CSEs in solid batteries. In this work, we fabricated open-structured LiLaTiO (LLTO) nanotubes (NTs) as ion-conductive fillers in CSEs by a gradient electrospinning method for the first time. Different from nanoparticles (NPs) and nanowires (NWs), our nanotubes are composed of connected small NPs, which offer three-dimensional (3D) Li-accessible pathways, large polymer/filler interfacial ionic conduction regions, and enhanced wettability against the polymer matrix. As a result, the solid electrolytes based on LLTO NTs and polyacrylonitrile (PAN) can display a high ionic conductivity of up to 3.6 × 10 S cm and a wide electrochemical window of 5 V at room temperature (RT). Furthermore, Li-Li symmetric cells using the LLTO NTs/PAN CSE can work stably over 1000 h with a polarization of 20 mV. LiFePO-Li full cells exhibit a high capacity of 142.5 mAh g with a capacity retention of 90% at 0.5 C after 100 cycles. All of these results demonstrate that the design of open-structured nanotubes as fillers is a promising strategy for high-performance solid electrolytes.
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http://dx.doi.org/10.1021/acsami.0c22635DOI Listing
March 2021

Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development.

Mol Cancer 2021 03 8;20(1):50. Epub 2021 Mar 8.

Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Background: The mRNA-based cancer vaccine has been considered a promising strategy and the next hotspot in cancer immunotherapy. However, its application on cholangiocarcinoma remains largely uncharacterized. This study aimed to identify potential antigens of cholangiocarcinoma for development of anti-cholangiocarcinoma mRNA vaccine, and determine immune subtypes of cholangiocarcinoma for selection of suitable patients from an extremely heterogeneous population.

Methods: Gene expression profiles and corresponding clinical information were collected from GEO and TCGA, respectively. cBioPortal was used to visualize and compare genetic alterations. GEPIA2 was used to calculate the prognostic index of the selected antigens. TIMER was used to visualize the correlation between the infiltration of antigen-presenting cells and the expression of the identified antigens. Consensus clustering analysis was performed to identify the immune subtypes. Graph learning-based dimensionality reduction analysis was conducted to visualize the immune landscape of cholangiocarcinoma.

Results: Three tumor antigens, such as CD247, FCGR1A, and TRRAP, correlated with superior prognoses and infiltration of antigen-presenting cells were identified in cholangiocarcinoma. Cholangiocarcinoma patients were stratified into two immune subtypes characterized by differential molecular, cellular and clinical features. Patients with the IS1 tumor had immune "hot" and immunosuppressive phenotype, whereas those with the IS2 tumor had immune "cold" phenotype. Interestingly, patients with the IS2 tumor had a superior survival than those with the IS1 tumor. Furthermore, distinct expression of immune checkpoints and immunogenic cell death modulators was observed between different immune subtype tumors. Finally, the immune landscape of cholangiocarcinoma revealed immune cell components in individual patient.

Conclusions: CD247, FCGR1A, and TRRAP are potential antigens for mRNA vaccine development against cholangiocarcinoma, specifically for patients with IS2 tumors. Therefore, this study provides a theoretical basis for the anti-cholangiocarcinoma mRNA vaccine and defines suitable patients for vaccination.
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http://dx.doi.org/10.1186/s12943-021-01342-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938044PMC
March 2021

Species and geographic specificity between endophytic fungi and host supported by parasitic Cynomorium songaricum and its host Nitraria tangutorum distributed in desert.

Arch Microbiol 2021 Mar 7. Epub 2021 Mar 7.

College of Pharmacy, Shaanxi University of Chinese Medicine, Century Avenue, Xianyang, 712046, Shaanxi, China.

This study was aimed to investigate whether host plant species and lifestyles, and environmental conditions in the desert affect endophytic fungi composition. Endophytic fungal communities from parasitic plant Cynomorium songaricum and its host Nitraria tangutorum were investigated from three sites including Tonggu Naoer, Xilin Gaole, and Guazhou in Tengger and Badain Jaran Deserts in China using the next-generation sequencing of a ribosomal RNA gene region. Similarity and difference in endophytic fungal composition from different geographic locations were evaluated through multivariate statistical analysis. It showed that plant genetics was a deciding factor affecting endophytic fungal composition even when C. songaricum and N. tangutorum grow together tightly. Not only that, the fungal composition was also greatly affected by the local environment and rainfall. However, the distribution and richness of fungal species indicated that the geographical distance exerted little influence on characterizing the fungal composition. Overall, the findings suggested that plant species, parasitic or non-parasitic lifestyles of the plant, and local environment strongly affected the number and diversity of the endophytic fungal species, which may provide valuable insights into the microbe ecology, symbiosis specificity, and the tripartite relationship among parasitic plant, host, and endophytic fungi, especially under desert environment.
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http://dx.doi.org/10.1007/s00203-021-02224-7DOI Listing
March 2021

Downregulation of miR‑146a inhibits osteoporosis in the jaws of ovariectomized rats by regulating the Wnt/β‑catenin signaling pathway.

Int J Mol Med 2021 Mar 30;47(3). Epub 2020 Dec 30.

Department of Orthopedics, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong 250031, P.R. China.

MicroRNAs (miRNAs or miRs) play important roles in osteoporosis and exhibit high potential in the therapeutic treatment of this condition. The present study aimed to explore the effects of miR‑146a on bone loss noted in the jawbones of ovariectomized (OVX) rats and the interaction of miR‑146a with the Wnt/β‑catenin signaling pathway. OVX Sprague‑Dawley female rats were used to establish the animal model of osteoporosis (OP). Bone mineral density (BMD) was measured via dual‑energy X‑ray and the miR‑146a levels were detected by reverse transcription‑quantitative PCR. miR‑146a antagonist (miR‑146a‑A) and negative control (miR‑146a‑NC) were used to examine the effects of miR‑146a on OVX rats. The contents of osteocalcin and tartrate resistant phosphatase (TRAP) were detected via ELISA. Hematoxylin and eosin, and TRAP staining were used to observe the pathological changes and the number of osteoclasts in the jawbone, respectively. In addition, the expression levels of the nuclear factor of activated T cells c1 (NFATc1), c‑Fos and cathepsin K (CTK) in the jawbone were detected by immunohistochemistry, whereas the expression levels of osteoprotegerin, TRAP, dickkopf1, Wnt2 and β‑catenin in the same tissues were assessed by western blot analysis. The Wnt2 activator (DKK2‑C2) and inhibitor (endostatin) were used to examine the effects of miR‑146a on the Wnt/β‑catenin pathway. The results indicated that the BMD was increased, whereas the contents of osteocalcin and TRAP were decreased in the miR‑146a‑A group compared with those noted in the OP or negative control groups (P<0.05). Although the trabecular bone area of the OP group was decreased, the conditions were improved in the miR‑146a‑A group. The number of osteoclasts was decreased in the miR‑146a‑A group compared with that noted in the OP group (P<0.05). The expression levels of NFATc1, c‑Fos and CTK in the miR‑146a‑A group were decreased compared with those noted in the OP or negative control groups (P<0.05). Similar results were found following the comparison of the miR‑146a‑A group with the DKK2‑C2 group. Taken together, these data demonstrated that miR‑146a downregulation inhibited OP of the jawbone in OVX rats by activating the Wnt/β‑catenin signaling pathway.
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http://dx.doi.org/10.3892/ijmm.2020.4839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834969PMC
March 2021

New two-dimensional arsenene polymorph predicted by first-principles calculation: Robust direct bandgap and enhanced optical adsorption.

Nanotechnology 2021 Mar 2. Epub 2021 Mar 2.

Institute of High Performance Computing, A*STAR, Singapore , Singapore, SINGAPORE.

In this work, we predict a new polymorph of two-dimensional (2D) monolayer arsenic. This structure, named as δ-As, consists of a centrosymmetric monolayer, which is thermodynamically and kinetically stable. Distinctly different from the previously predicted monolayer arsenic with indirect band gap, the new allotrope exhibits direct band gap characteristic. Moreover, while keeping the direct band gap unchanged, the band gap of monolayer δ-As can be adjusted from 1.83 eV to 0 eV by applying zigzag-direction tensile strain, which is pronounced advantage for solar cell and photodetector applications.
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http://dx.doi.org/10.1088/1361-6528/abeb3aDOI Listing
March 2021

Identification of tumor antigens and immune subtypes of pancreatic adenocarcinoma for mRNA vaccine development.

Mol Cancer 2021 03 1;20(1):44. Epub 2021 Mar 1.

Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310003, Hangzhou, China.

Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against pancreatic adenocarcinoma (PAAD) remains undefined. Accumulating evidence suggests that immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potent antigens in PAAD for mRNA vaccine development, and further distinguish immune subtypes of PAAD to construct an immune landscape for selecting suitable patients for vaccination.

Methods: Gene expression profiles and clinical information of 239 PAAD datasets were extracted from ICGC, and RNA-Seq data of 103 samples were retrieved from TCGA. GEPIA was used to calculate differential expression levels and prognostic indices, cBioPortal program was used to compare genetic alterations, and TIMER was used to explore correlation between genes and immune infiltrating cells. Consensus cluster was used for consistency matrix construction and data clustering, DAVID was used for functional annotation, and graph learning-based dimensional reduction was used to depict immune landscape.

Results: Six overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in PAAD, including ADAM9, EFNB2, MET, TMOD3, TPX2, and WNT7A. Furthermore, five immune subtypes (IS1-IS5) and nine immune gene modules of PAAD were identified that were consistent in both patient cohorts. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to the other subtypes. IS4 and IS5 tumors were immunologically cold and associated with higher tumor mutation burden. Immunogenic cell death modulators, immune checkpoints, and CA125 and CA199, were also differentially expressed among the five immune subtypes. Finally, the immune landscape of PAAD showed a high degree of heterogeneity between individual patients.

Conclusions: ADAM9, EFNB2, MET, TMOD3, TPX2, and WNT7A are potent antigens for developing anti-PAAD mRNA vaccine, and patients with IS4 and IS5 tumors are suitable for vaccination.
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http://dx.doi.org/10.1186/s12943-021-01310-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917175PMC
March 2021

Research on fault detection of asymmetric piecewise well-posed stochastic resonance system.

Rev Sci Instrum 2021 Feb;92(2):025116

School of Optoelectronic Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

Stochastic resonance of an asymmetric piecewise well-posed system driven by a periodic forcing and Gaussian white noise is investigated. Aiming at the problem that the output saturation of the classical stochastic resonance (CSR) system needs to be further improved, the dimensionality of the quartic function is reduced to a quadratic function, and the well position of the function becomes asymmetric. First, the potential function and mean first passage time are analyzed, and then the signal to noise ratio formula of the system is derived through adiabatic approximation theory. Second, the system is simulated and tested. Theoretical analysis and numerical simulation show that the system in a well-posed symmetric case has better performance than the CSR system, but is better in a well-posed asymmetric case. Finally, the bearing fault detection is processed by using the proposed system. The results show that the fault frequency can be more accurately identified by the well-posed asymmetry, and the energy of the characteristic signal can be improved further. The theoretical basis and reference value of the system are provided for further application in practical engineering testing.
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http://dx.doi.org/10.1063/5.0041204DOI Listing
February 2021

Rice calcium/calmodulin-dependent protein kinase directly phosphorylates a mitogen-activated protein kinase kinase to regulate abscisic acid responses.

Plant Cell 2021 Feb 25. Epub 2021 Feb 25.

College of Life Sciences, National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Crop Physiology Ecology and Production Management, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.

Ca2+/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of abscisic acid (ABA) and abiotic stress signaling in plants and is believed to act upstream of mitogen-activated protein kinase (MAPK) in ABA signaling. However, it is unclear how CCaMK activates MAPK in ABA signaling. Here, we show that OsDMI3, a rice (Oryza sativa) CCaMK, directly interacts with and phosphorylates OsMKK1, a MAPK kinase (MKK) in rice, in vitro and in vivo. OsDMI3 was found to directly phosphorylate Thr-25 in the N-terminus of OsMKK1, and this Thr-25 phosphorylation is OsDMI3-specific in ABA signaling. The activation of OsMKK1 and its downstream kinase OsMPK1 is dependent on Thr-25 phosphorylation of OsMKK1 in ABA signaling. Moreover, ABA treatment induces phosphorylation in the activation loop of OsMKK1, and the two phosphorylations, in the N-terminus and in the activation loop, are independent. Further analyses revealed that OsDMI3-mediated phosphorylation of OsMKK1 positively regulates ABA responses in seed germination, root growth, and tolerance to both water stress and oxidative stress. Our results indicate that OsMKK1 is a direct target of OsDMI3, and OsDMI3-mediated phosphorylation of OsMKK1 plays an important role in activating the MAPK cascade and ABA signaling.
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http://dx.doi.org/10.1093/plcell/koab071DOI Listing
February 2021

Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy.

Signal Transduct Target Ther 2021 Feb 20;6(1):72. Epub 2021 Feb 20.

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, Zhejiang, China.

Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon in the armory of cancer therapy. Accumulating evidence suggests that the tumor immune microenvironment plays a critical role in anti-cancer immunity, which may result in immune checkpoint blockade therapy being ineffective, in addition to other novel immunotherapies in cancer patients. In the present review, we discuss the deficiencies of current cancer immunotherapies. More importantly, we highlight the critical role of tumor immune microenvironment regulators in tumor immune surveillance, immunological evasion, and the potential for their further translation into clinical practice. Based on their general targetability in clinical therapy, we believe that tumor immune microenvironment regulators are promising cancer immunotherapeutic targets. Targeting the tumor immune microenvironment, alone or in combination with immune checkpoint-targeting drugs, might benefit cancer patients in the future.
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http://dx.doi.org/10.1038/s41392-020-00449-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896069PMC
February 2021

Clinicopathological characteristics of extranodal follicular dendritic cell sarcoma: A report of two cases.

Oncol Lett 2021 Mar 6;21(3):182. Epub 2021 Jan 6.

Department of General Surgery IV, Baoding First Hospital, Baoding, Hebei 071000, P.R. China.

Follicular dendritic cell sarcoma (FDCS) is an extremely rare tumor, which mainly originates from FDCs in the lymph nodes. Sometimes FDCS can arise from outside the lymph nodes due to the existence of acquired lymphoid tissue, which becomes the histological basis of the tumor. The diagnosis of FDCS, particularly extranodal FDCS, presents a challenge for pathologists and hematopathologists. The present study presents two cases of extranodal FDCS based on clinical features and histomorphology. Soft tissue of the chest wall was involved in case 1 and right tonsil tissue in case 2. Case 1 underwent surgery, and was in good health post-operatively. During the 5-month post-operative follow-up period, the patient was healthy in all respects. Case 2 received surgery combined with radiotherapy, and the follow-up data reported that the patient remained alive, without signs of recurrence or metastasis during the 4-month post-operative follow-up period. Additionally, a total of 102 cases of extranodal FDCS were retrieved from the literature, which were extracted and reviewed carefully. The rates of recurrence, metastasis and mortality were 14.63 (12/82), 17.07 (14/82) and 8.29% (15/82), respectively. The overall survival rates of the 102 cases, showing 2-year total survival rates, were 70%, the same with that of 5-year total survival rates. The 2-year tumor-free total survival rates were 68%, and the 5-year equivalents were 32%. Female patients had a poorer prognosis than male patients (P<0.05). Kaplan-Meier estimation presented no statistically significant differences between disease-free survival rates or overall survival rates and age, tumor size or treatment (P>0.05).
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http://dx.doi.org/10.3892/ol.2021.12443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816366PMC
March 2021

Effects of tea tree oil supplementation on growth performance, antioxidant capacity, immune status and microbial community in weaned pigs.

Arch Anim Nutr 2021 Apr 8;75(2):121-136. Epub 2021 Feb 8.

State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre, China Agricultural University, Beijing, China.

The objective of this study was to determine whether dietary tea tree oil (TTO) supplementation could effectively replace the antibiotics through modulating the antioxidant capacity and intestinal microbiota profile, and then decreasing the diarrhoea incidence and improving the growth performance of weaned pigs. A total of 216 weaned pigs with initial body weights (BW) of 9.19 ± 1.86 kg were randomly allocated to three dietary treatments in a completely randomised design. The dietary treatments included a corn-soybean meal basal diet (CON) without any antibiotics, and two experimental diets formulated by adding 75 mg/kg aureomycin (AGP) or 100 mg/kg TTO into the basal diet, respectively. Pigs fed the TTO diet showed greater gain to feed ratio ( < 0.05) than those fed CON and AGP diets during d 0-14 and d 14-28. Both dietary TTO and AGP supplementation tended to increase the average daily gain of weaned pigs during d 14-28 ( = 0.06) and the overall 28-d period ( = 0.07), and significantly reduced ( < 0.05) the diarrhoea incidence during d 0-14 compared with the CON treatment. In addition, dietary TTO supplementation improved the apparent total tract digestibility of dry matter and ether extract ( < 0.05), and increased ( < 0.05) the propionate and butyrate concentrations in faecal samples of weaned pigs. Moreover, pigs fed the TTO diet showed greater total antioxidant capacity, greater superoxide dismutase and interleukin-10 concentrations, and lower malondialdehyde concentration in serum than those fed the CON diet ( < 0.05). Furthermore, pigs fed the TTO diet demonstrated greater relative abundance of _, while those fed the AGP diet exhibited greater relative abundance of at family level. In conclusion, dietary TTO supplementation could improve growth performance in weaned pigs, which could be mainly attributed to the benefits on nutrient digestibility, antioxidative capacity and microbial community profile.
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http://dx.doi.org/10.1080/1745039X.2021.1877074DOI Listing
April 2021

Killing HIV-infected resting central memory CD4 T cells by targeting inhibitor of apoptosis proteins-inhibited autophagy.

Antivir Chem Chemother 2021 Jan-Dec;29:2040206620980888

Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Dysfunction of CD4 T cells by HIV infection can cause serious immune defects. Recently, Campbell and colleagues described an intriguing and simple therapeutic method for HIV-infected resting central memory CD4 T cells (HIV-T), dependently on inhibitor of apoptosis (IAP) family proteins-targeted and second mitochondria-derived activator of caspases (SMAC) mimetics-mediated apoptosis, which is only triggered in HIV-T and not uninfected ones. Autophagy induction and subsequent formation of a ripoptosome-like death signaling complex were observed after such treatment, which may partially explain the potential mechanism. However, the direct intracellular inhibitory effects of IAPs on autophagy, as well as the critical roles of autophagy in activating extracellular anti-infection immune responses, warrant further investigation. Thus, this pointer aims to provide potential alternative mechanisms and to suggest important avenues for follow-up study.
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http://dx.doi.org/10.1177/2040206620980888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876937PMC
February 2021

Using electrical impedance tomography for rapid determination of starch and soluble sugar contents in Rosa hybrida.

Sci Rep 2021 Feb 3;11(1):2871. Epub 2021 Feb 3.

College of Electrical and Mechanical Engineering, Hebei Agricultural University, Baoding, 071000, Hebei, China.

Soluble sugars and starches are important metabolites of plant life and physiological markers of plant stress response. There is an urgent need to develop a non-destructive and rapid method for determining plant starch and soluble sugar contents. Electrical impedance tomography (EIT) technology has been used to determine the physiological state and cold resistance of select plant tissues. However, so far there have been no reports on the use of EIT for the rapid estimation of soluble sugar and starch contents. In this study, EIT was used to obtain reconstructed voltage values and estimate starch and soluble sugar contents in the stems of three Rosa hybrida cultivars during February to May, which were grown in the Specimen Park (38° 50' N, 115° 26' E) of Hebei Agricultural University, Baoding City, Hebei Province, China. Stems from two of the cultivars were used for establishing regression models for starch and soluble sugar contents as functions of reconstructed voltage values. The third cultivar was used to test the accuracy of the regression models. The quadratic regression model was best for determining soluble sugar content and the logarithmic regression model was best for determining starch content. Thus, this research provided technical support for using EIT to analyze changes in physiological parameters and to rapidly estimate physiological indexes of plants. More studies were now needed to validate the results in this paper.
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http://dx.doi.org/10.1038/s41598-021-82456-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859186PMC
February 2021

Cerebrovascular disease in pregnancy and puerperium: perspectives from neuroradiologists.

Quant Imaging Med Surg 2021 Feb;11(2):838-851

Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Pregnancy-related cerebrovascular disease is a serious complication of pregnancy and puerperium. The etiology and pathological mechanisms of cerebrovascular disease are complex, involving changes in the cardiovascular, endocrine, and immune systems. Vascular risk factors during pregnancy and puerperium may cause vasospasm and endothelial cell damage leading to cerebral ischemia, hemorrhage, posterior reversible encephalopathy syndrome (PRES), and reversible cerebral vasoconstriction syndrome. Arterial or venous obstruction may damage the blood-brain barrier (BBB) and impede venous return, resulting in cerebral edema, hemorrhage, and intracranial hypertension. Pregnancy with hypercoagulability may threaten the lives of both the mother and the developing fetus. With improvements in stroke treatment during pregnancy and puerperium, neuroradiologists have gained new insights into this problem. This article reviews the pathogenesis, imaging findings, and risk factors of stroke during pregnancy and puerperium, focusing on imaging diagnosis and prognostic assessment.
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http://dx.doi.org/10.21037/qims-20-830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779914PMC
February 2021

Helmet chinstrap protective role in maxillofacial blast injury.

Technol Health Care 2020 Nov 13. Epub 2020 Nov 13.

Background: The protective role of helmet accessories in moderating stress load generated by explosion shock waves of explosive devices is usually neglected.

Objective: In the presented study, the protective role of the helmet chinstrap against the impulse and overpressure experienced by the maxillofacial region were examined.

Methods: The explosion shock wave and skull interaction were investigated under three different configurations: (1) unprotected skull, (2) skull with helmet (3) skull with helmet and chinstrap. For this purpose, a 3D finite element model (FEM) was constructed to mimic the investigated biomechanics module. Three working conditions were set according to different explosive charges and distances to represent different load conditions. Case 1: 500 mg explosive trinitrotoluene (TNT), 3 cm, case 2: 1000 mg TNT, 3 cm, and case 3: 1000 mg TNT and 6 cm distance to the studied object. The explosion effect was discussed by examining the shock wave stress flow pattern. Three points were selected on the skull and the stress curve of each point position were illustrated for each case study.

Results: The results showed that the helmet chinstrap can reduce the explosive injuries and plays a protective role in the maxillofacial region, especially for the mandible.
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http://dx.doi.org/10.3233/THC-202406DOI Listing
November 2020

Electron cloud migration effect-induced lithiophobicity/lithiophilicity transformation for dendrite-free lithium metal anodes.

Nanoscale 2021 Feb 29;13(5):3027-3035. Epub 2021 Jan 29.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, School of Materials Science and Engineering, Wuhan University of Technology, Luoshi Road 122, Wuhan, 430070, P. R. China.

Enabling stable lithium metal anodes is significant for developing electrochemical energy storage systems with higher energy density. However, safety hazards, infinite volume expansion, and low coulombic efficiency (CE) of lithium metal anodes always hinder their practical application. Herein, a nano-thickness lithiophilic Cu-Ni bimetallic coating was synthesized to prepare dendrite-free lithium metal anodes. The electron cloud migration effect caused by the different electronegativities of Cu and Ni can achieve lithiophobicity/lithiophilicity transformation and thus promote uniform Li deposition/dissolution. By changing the ratio of Cu to Ni, the electron cloud migration can be reasonably adjusted for obtaining dendrite-free lithium anodes. As a result, the as-obtained Cu-Ni bimetallic coating is able to guarantee dendrite-free lithium metal anodes with a stable long cycling time (>1500 hours) and a small voltage hysteresis (∼26 mV). In addition, full cells with LiFePO as a cathode present excellent cycling stability and high coulombic efficiency. This work can open a new avenue for optimizing the lithiophilicity of materials and realizing dendrite-free anodes.
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http://dx.doi.org/10.1039/d0nr08343gDOI Listing
February 2021

Analysis of synonymous codon usage of transcriptome database in .

PeerJ 2021 4;9:e10450. Epub 2021 Jan 4.

College of Traditional Chinese Medicine, Hebei University, Baoding, China.

Background: is an endangered and important medicinal plant in Asian countries, especially in China. However, there is little knowledge about the codon usage bias for CDSs. In this project, codon usage bias was determined based on the 2,626 predicted CDSs from R. palmatum transcriptome.

Methods: In this study, all codon usage bias parameters and nucleotide compositions were calculated by Python script, Codon W, DNA Star, CUSP of EMBOSS.

Results: The average GC and GC3 content are 46.57% and 46.6%, respectively, the results suggested that there exists a little more AT than GC in the genes, and the codon bias of genes preferred to end with A/T. We concluded that the codon bias in was affect by nucleotide composition, mutation pressure, natural selection, gene expression levels, and the mutation pressure is the prominent factor. In addition, we figured out 28 optimal codons and most of them ended with A or U. The project here can offer important information for further studies on enhancing the gene expression using codon optimization in heterogeneous expression system, predicting the genetic and evolutionary mechanisms in .
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http://dx.doi.org/10.7717/peerj.10450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789865PMC
January 2021

Safety and efficacy of prostatic artery embolization for large benign prostatic hyperplasia in elderly patients.

J Int Med Res 2021 Jan;49(1):300060520986284

Department of Urology, the Ninth People's Hospital of Suzhou City, Suzhou, China.

Objective: To assess the safety and efficacy of prostatic arterial embolization (PAE) for elderly patients with lower urinary tract symptoms secondary to large benign prostatic hyperplasia.

Methods: Twenty-eight patients (>80 years of age) with prostate volume >80 mL were enrolled from October 2016 to October 2019. PAE was performed using microspheres and functional results were evaluated at 1, 3, 6, and 12 months postoperatively. The following data were recorded: International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urine flow rate (Qmax), post-void residual urine volume, prostate volume and total prostate-specific antigen level.

Results: Selective prostatic arterial catheterization and embolization were achieved in 27 of 28 patients. Follow-up data were available for those 27 patients until 12 months postoperatively. Significant improvements were found at all postoperative time points in terms of the mean IPSS, mean QoL score, mean Qmax, mean post-void residual urine volume, mean total prostate-specific antigen level, and mean prostate volume. The overall complication rate was 46.4%.

Conclusions: PAE is an efficacious and safe treatment for elderly patients with large prostate volume; it may offer an effective approach for patients who are not candidates for open or endoscopic surgical procedures because of comorbidities.
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http://dx.doi.org/10.1177/0300060520986284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844465PMC
January 2021

Upregulation of KIF11 in TP53 Mutant Glioma Promotes Tumor Stemness and Drug Resistance.

Cell Mol Neurobiol 2021 Jan 25. Epub 2021 Jan 25.

Department of Neurosurgery Six, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China.

Glioma is the most common type of primary brain malignancy with high morbidity and mortality, but little is known about its pathological mechanisms. Kinesin family member 11 (KIF11) is a key driver of malignancy in glioblastoma, a grade IV glioma, but its involvement in glioma chemoresistance remains to be determined. We accessed the TCGA open datasets, collected glioma tumor tissue samples, and analyzed the expression of KIF11 in glioma patients. Meanwhile, the correlation between KIF11 and survival outcomes was determined by the Kaplan-Meier analysis. The role of KIF11 in glioma tumor cell function was assessed in an in vitro knockdown and overexpressing system. Here, we found that KIF11 was upregulated in glioma tumors and negatively correlated with overall survival outcomes via analyzing the open datasets. KIF11 was negatively correlated with TP53 expression. Furthermore, KIF11 promoted the stemness in glioma cells, accompanied by increased cell proliferation and chemoresistance. Mechanistically, we found that KIF11 promoted cell cycle progression via upregulating cyclin expression.
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http://dx.doi.org/10.1007/s10571-020-01038-3DOI Listing
January 2021

A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells.

Eur J Med Chem 2021 Mar 2;213:113148. Epub 2021 Jan 2.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, United States; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, 91125, United States. Electronic address:

Small-molecule inhibitors of p97 are useful tools to study p97 function. Human p97 is an important AAA ATPase due to its diverse cellular functions and implication in mediating the turnover of proteins involved in tumorigenesis and virus infections. Multiple p97 inhibitors identified from previous high-throughput screening studies are thiol-reactive compounds targeting Cys522 in the D2 ATP-binding domain. Thus, these findings suggest a potential strategy to develop covalent p97 inhibitors. We first used purified p97 to assay several known covalent kinase inhibitors to determine if they can inhibit ATPase activity. We evaluated their selectivity using our dual reporter cells that can distinguish p97 dependent and independent degradation. We selected a β-nitrostyrene scaffold to further study the structure-activity relationship. In addition, we used p97 structures to design and synthesize analogues of pyrazolo[3,4-d]pyrimidine (PP). We incorporated electrophiles into a PP-like compound 17 (4-amino-1-tert-butyl-3-phenyl pyrazolo[3,4-d]pyrimidine) to generate eight compounds. A selective compound 18 (N-(1-(tert-butyl)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)acrylamide, PPA) exhibited excellent selectivity in an in vitro ATPase activity assay: IC of 0.6 μM, 300 μM, and 100 μM for wild type p97, yeast Cdc48, and N-ethylmaleimide sensitive factor (NSF), respectively. To further examine the importance of Cys522 on the active site pocket during PPA inhibition, C522A and C522T mutants of p97 were purified and shown to increase IC values by 100-fold, whereas replacement of Thr532 of yeast Cdc48 with Cysteine decreased the IC by 10-fold. The molecular modeling suggested the hydrogen bonds and hydrophobic interactions in addition to the covalent bonding at Cys522 between WT-p97 and PPA. Furthermore, tandem mass spectrometry confirmed formation of a covalent bond between Cys522 and PPA. An anti-proliferation assay indicated that the proliferation of HCT116, HeLa, and RPMI8226 was inhibited by PPA with IC of 2.7 μM, 6.1 μM, and 3.4 μM, respectively. In addition, PPA is able to inhibit proliferation of two HCT116 cell lines that are resistant to CB-5083 and NMS-873, respectively. Proteomic analysis of PPA-treated HCT116 revealed Gene Ontology enrichment of known p97 functional pathways such as the protein ubiquitination and the ER to Golgi transport vesicle membrane. In conclusion, we have identified and characterized PPA as a selective covalent p97 inhibitor, which will allow future exploration to improve the potency of p97 inhibitors with different mechanisms of action.
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http://dx.doi.org/10.1016/j.ejmech.2020.113148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954469PMC
March 2021

8-cyanobenzothiazinone analogs with potent antitubercular activity.

Med Chem Res 2021 Jan 13:1-10. Epub 2021 Jan 13.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050 China.

8-Nitrobenzothiazinones (BTZs) exemplified by macozinone are a new class of antitubercular agents with exceptionally potent activity. The aryl nitro group has been considered indispensable for activity since this is bioactivated within mycobacteria by the flavoenzyme DprE1 to a reactive nitroso metabolite that covalently labels Cys387. However, the aryl nitro group is a potential liability with regards to safety, stability, and resistance. In this paper, we introduced a nitrile as a bioisosteric replacement of the nitro group, which we hypothesize can maintain a similar covalent mechanism of inhibition, but mitigate against the aforementioned concerns. 8-cyanobenzothiazinone displayed potent antitubercular activity with an MIC of 130 nM and had an improved volume of distribution in mice that increased the intrinsic half-life by twofold compared to macozinone. Analysis of the C-2 substituent of revealed similar structure-activity relationships as observed for macozinone. Overall, the results confirm the 8-nitro group of benzothiazinones can be successfully replaced with a nitrile to retain useful activity and favorable pharmacokinetic properties.
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http://dx.doi.org/10.1007/s00044-020-02676-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805566PMC
January 2021

The complete chloroplast genome of (Rose) D.R.Hunt.

Mitochondrial DNA B Resour 2020 Jul 24;5(3):2932-2933. Epub 2020 Jul 24.

College of Pharmacy, Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine, Shaanxi University of Chinese Medicine, Xi'an, China.

In this study, the complete chloroplast genome of (Rose) D.R.Hunt was investigated. The whole chloroplast genome sequence is 166,086 bp in length, which consists of a 94,376 bp large single copy (LSC) and an 18,678 bp small single copy (SSC) regions, separated by a pair of 26,518 bp inverted repeat (IR) regions. The chloroplast genome of encodes 131 annotated known unique genes including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on chloroplast genome sequences demonstrated that is most closely related to .
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http://dx.doi.org/10.1080/23802359.2020.1787262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782135PMC
July 2020

Reviving the role of MET in liver cancer therapy and vaccination: an autophagic perspective.

Oncoimmunology 2020 09 13;9(1):1818438. Epub 2020 Sep 13.

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Past failures in clinical trials have dampened the enthusiasm for studying the HGF receptor MET and postponed the development of MET-targeted drugs for cancer therapy. However, new evidence suggests that, at least in liver cancer, MET is still a promising therapeutic target, and may also be a potential target for cancer vaccines. This paper briefly highlights novel research advances in this rapidly-evolving field in the perspective of autophagy, and discusses future directions for further investigation of MET-based cancer therapy and vaccination.
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http://dx.doi.org/10.1080/2162402X.2020.1818438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781811PMC
September 2020

Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors.

Med Chem Res 2021 Jan 12:1-12. Epub 2021 Jan 12.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xiannongtan Street, Beijing, 100050 China.

Herein we report our investigation concerning the development of Human neutrophil elastase (hNE) inhibitors for the treatment of Acute Respiratory Distress Syndrome (ARDS). Various benzenesulfonic acid derived compounds were synthesized and evaluated as competitive inhibitors of hNE. Biological screening revealed that compound shows moderate inhibitory activity (IC = 35.2 μM) against hNE. Compound was also superimposed onto the active center of hNE to understand the binding mode.
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http://dx.doi.org/10.1007/s00044-020-02684-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801566PMC
January 2021