Publications by authors named "Chao Gu"

156 Publications

miR-194-5p down-regulates tumor cell PD-L1 expression and promotes anti-tumor immunity in pancreatic cancer.

Int Immunopharmacol 2021 Jun 4;97:107822. Epub 2021 Jun 4.

Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Tianjin Medical University, Tianjin, China. Electronic address:

Pancreatic cancer is a highly malignant cancer of the digestive tract. Studies have shown that in some types of cancer, a high level of microRNA-194-5p (miR-194-5p) is beneficial for controlling tumor progression, while in other cancers it plays a completely opposite role. However, how miR-194-5p affects anti-tumor immunity of pancreatic cancer remains unclear. In this study, we found that high expression of miR-194-5p in human pancreatic cancer patients is associated with a better survival rate, while increased expression of programmed cell death ligand 1 (PD-L1) in human pancreatic cancer patients is associated with a worse survival rate. In pancreatic cancer, the expression level of PD-L1 is negatively correlated with the expression level of miR-194-5p, and we identified that PD-L1 was target gene of miR-194-5p. In addition, we found that overexpression of miR-194-5p inhibited the migration, invasion and proliferation of pancreatic cancer cells in vitro. The orthotopic mouse model of pancreatic cancer shown that miR-194-5p suppressed the progression of pancreatic cancer, promoted the infiltration of CD8 T cells in tumor immune microenvironments, and enhanced the IFN-γ production of CD8 T cells. Consistently, the co-culture experiments showed that overexpression of miR-194-5p in tumor cell enhanced IFN-γ production by CD8 T cells. In conclusion, miR-194-5p may serve as a novel immunotherapeutic target for pancreatic ductal adenocarcinoma (PDAC) by inhibiting the expression of PD-L1, and play important roles in inhibiting the progression of pancreatic cancer and boosting the anti-tumor effect of CD8 T cells.
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http://dx.doi.org/10.1016/j.intimp.2021.107822DOI Listing
June 2021

polysaccharides alleviate cognitive decline in aging model mice by restoring the gut microbiota-brain axis.

Aging (Albany NY) 2021 Jun 3;13. Epub 2021 Jun 3.

Inner Mongolia Medical University, Hohhot 010110, China.

Recent evidence suggests alterations in the gut microbiota-brain axis may drive cognitive impairment with aging. In the present study, we observed that prolonged administration of D-galactose to mice induced cognitive decline, gut microbial dysbiosis, peripheral inflammation, and oxidative stress. In this model of age-related cognitive decline, polysaccharides (CDPS) improved cognitive function in D-galactose-treated mice by restoring gut microbial homeostasis, thereby reducing oxidative stress and peripheral inflammation. The beneficial effects of CDPS in these aging model mice were abolished through ablation of gut microbiota with antibiotics or immunosuppression with cyclophosphamide. Serum metabolomic profiling showed that levels of creatinine, valine, L-methionine, o-Toluidine, N-ethylaniline, uric acid and proline were all altered in the aging model mice, but were restored by CDPS. These findings demonstrated that CDPS improves cognitive function in a D-galactose-induced aging model in mice by restoring homeostasis of the gut microbiota-brain axis, which alleviated an amino acid imbalance, peripheral inflammation, and oxidative stress. CDPS thus shows therapeutic potential for patients with memory and learning disorders, especially those related to gut microbial dysbiosis.
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http://dx.doi.org/10.18632/aging.203090DOI Listing
June 2021

ZNRF2 attenuates focal cerebral ischemia/reperfusion injury in rats by inhibiting mTORC1-mediated autophagy.

Exp Neurol 2021 Aug 13;342:113759. Epub 2021 May 13.

Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Zinc and ring finger 2 (ZNRF2), an E3 ubiquitin ligase, plays a crucial role in many diseases. However, its role in cerebral ischemia/reperfusion injury (CIRI) still remains unknown. In this study, the function and molecular mechanism of ZNRF2 in CIRI in vivo and vitro was studied. ZNRF2 was found to be dramatically downregulated in CIRI. Overexpression of ZNRF2 could significantly reduce the neurological deficit, brain infarct volume and histopathological damage of cortex in middle cerebral artery occlusion/reperfusion. Concomitantly, overexpression of ZNRF2 increased the primary neuronal viability and decreased the neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Mechanistically, overexpression of ZNRF2 inhibited the over-induction of autophagy induced by OGD/R which was abolished by mTORC1 inhibitor rapamycin. It can be concluded that ZNRF2 plays a protective effect in CIRI and the underlying mechanism may be related to the inhibition of mTORC1-mediated autophagy.
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http://dx.doi.org/10.1016/j.expneurol.2021.113759DOI Listing
August 2021

Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming.

Aging Cell 2021 May 8:e13375. Epub 2021 May 8.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Although its pathogenesis remains unclear, a number of studies indicate that microglia-mediated neuroinflammation makes a great contribution to the pathogenesis of PD. Melatonin receptor 1 (MT1) is widely expressed in glia cells and neurons in substantia nigra (SN). Neuronal MT1 is a neuroprotective factor, but it remains largely unknown whether dysfunction of microglial MT1 is involved in the PD pathogenesis. Here, we found that MT1 was reduced in microglia of SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Microglial MT1 activation dramatically inhibited lipopolysaccharide (LPS)-induced neuroinflammation, whereas loss of microglial MT1 aggravated it. Metabolic reprogramming of microglia was found to contribute to the anti-inflammatory effects of MT1 activation. LPS-induced excessive aerobic glycolysis and impaired oxidative phosphorylation (OXPHOS) could be reversed by microglial MT1 activation. MT1 positively regulated pyruvate dehydrogenase alpha 1 (PDHA1) expression to enhance OXPHOS and suppress aerobic glycolysis. Furthermore, in LPS-treated microglia, MT1 activation decreased the toxicity of conditioned media to the dopaminergic (DA) cell line MES23.5. Most importantly, the anti-inflammatory effects of MT1 activation were observed in LPS-stimulated mouse model. In general, our study demonstrates that MT1 activation inhibits LPS-induced microglial activation through regulating its metabolic reprogramming, which provides a mechanistic insight for microglial MT1 in anti-inflammation.
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http://dx.doi.org/10.1111/acel.13375DOI Listing
May 2021

Soft chemistry of metastable metal chalcogenide nanomaterials.

Chem Soc Rev 2021 May 4. Epub 2021 May 4.

Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Institute of Energy, Hefei Comprehensive National Science Center, CAS Center for Excellence in Nanoscience, Department of Chemistry, Institute of Biomimetic Materials & Chemistry, Anhui Engineering Laboratory of Biomimetic Materials, University of Science and Technology of China, Hefei, 230026, China.

The metastable nature of metal chalcogenide nanomaterials (MCNs) provides us with fresh perspectives and plentiful grounds in the search of new strategies for physicochemical tuning. In the past decade, numerous efforts have been devoted to synthesizing and modifying diverse emerging MCNs based on their "soft chemistry", that is, gently regulating the composition, structure, phase, and interface while not entirely disrupting the original features. This tutorial review focuses on design principles based on the metastability of MCNs, such as ion mobility and vacancy, thermal and structural instability, chemical reactivity, and phase transition, together with corresponding soft chemical approaches, including ion-exchange, catalytic growth, segregation or coupling, template grafting or transformation, and crystal-phase engineering, and summarizes recent advances in their preparation and modification. Finally, prospects for the future development of soft chemistry-directed synthetic guidelines and metastable metal chalcogenide-derived nanomaterials are proposed and highlighted.
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http://dx.doi.org/10.1039/d0cs00881hDOI Listing
May 2021

Actein antagonizes colorectal cancer through blocking PI3K/Akt pathways by downregulating IMPDH2.

Anticancer Drugs 2021 Apr 23. Epub 2021 Apr 23.

Anorectal Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine College of Health, Shandong University of Traditional Chinese Medicine Preventive Medicine Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Background: Actein, a triterpene glycoside, isolated from rhizomes of Cimicifuga foetida, was reported to exhibit anticancer effects in vitro and in vivo. However, the effects of actein on colorectal cancer (CRC) remains unclear. As one of the most popular cancers all over the world, CRC ranked third place in both men and women. Recently, we investigated the potential anti-CRC effects of actein and its mechanisms.

Methods: The Cell counting kit-8 cell proliferation assays, cell cycle detection, apoptosis detection, reactive oxygen species and mitochondrial membrane potential evaluation, western blot, as well as SW480 xenograft mice model were conducted to illustrate the mechanisms of action on anti-CRC effects of actein.

Results: Actein could significantly inhibit the human CRC cell lines SW480 and HT-29 proliferation, whereas less antiproliferation effects were found in normal colorectal cell lines HCoEpiC and FHC. Administration of actein resulted in G1 phase cell cycle arrest in both SW480 and HT-29 cells. Moreover, mitochondria-mediated apoptosis was also observed after treatment with actein in SW480 and HT-29 cell lines. Further investigation of mechanisms of action on actein-mediated anti-CRC proliferation effects indicated that the phosphoinositide 3-kinases (PI3K)/Akt pathways were involved. Actein significantly downregulated the phosphorylation of key molecules in PI3K/Akt pathways, including mTOR, glycogen synthesis kinase 3β (GSK-3β), as well as FOXO1. In addition, inosine 5'-monophosphate dehydrogenase type II (IMPDH2) was also observed decreasing in both SW480 and HT-29 cell lines after actein treatment, suggesting that actein may inhibit the PI3K/Akt pathways by decreasing IMPDH2. Finally, our SW480 xenograft model verified the anti-CRC effects and the safety of actein in vivo.

Summary: Our findings suggest actein is worthy of further investigation as a novel drug candidate for the treatment of CRC.
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http://dx.doi.org/10.1097/CAD.0000000000001080DOI Listing
April 2021

Tenacissoside G synergistically potentiates inhibitory effects of 5-fluorouracil to human colorectal cancer.

Phytomedicine 2021 Jun 23;86:153553. Epub 2021 Mar 23.

Department of Clinical Pharmacology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address:

Background: Colorectal cancer (CRC) is one of the most malignant tumors worldwide with poor prognosis and low survival rate. Since the clinical efficacy of the commonly used 5-fluorouracil (5-FU) based chemotherapy in CRC patients is limited because of its intolerable adverse effects, there is an urgent need to explore agents that can enhance the anti-cancer activity of 5-FU, reduce adverse effects and prevent resistance.

Purpose: This study aims to investigate Tenacissoside G (TG)'s synergistic potentiation with 5-FU in inhibitory activity to colorectal cancer cells.

Methods: The anti-proliferation effect of TG on 5 colorectal cancer cell lines was assessed by CCK-8 assay. The isobologram analysis and combination index methods were used to detect the synergistic effect of TG and 5-FU by the CompuSyn software using the T.C. Chou Method. The effects of TG/5-FU combination on cell cycle distribution and apoptosis induction were detected by flow cytometry. DNA damage degrees of cells treated with TG, 5-FU and their combination were evaluated by the alkaline comet assay. Protein expression regulated by the TG/5-FU combination was investigated by western blotting. Furthermore, a xenograft mouse model was established to investigate the synergistic anti-tumor effect in vivo.

Results: In this work, we observed a dose-dependent growth inhibitory activity and cell cycle arrest induction of TG, a monomeric substance originated from Marsdenia tenacissima (Roxb.) Wight et Arn, in colorectal cancer cells. It was found that TG potentiated the anticancer effects of 5-FU with a synergism for the first time. And the co-treatment effects were also validated by in vivo experiments. The underlying mechanisms involved in the synergistic effects were probably included: (1) increased activation of caspase cascade; (2) enhancement of DNA damage degree and (3) induction of p53 phosphorylation at Serine 46.

Conclusion: TG potentiated 5-FU's inhibitory activity to human colorectal cancer through arresting cell cycle progression and inducing p53-mediated apoptosis, which may present a novel strategy in CRC therapies and contribute to the optimizing clinical application of 5-FU.
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http://dx.doi.org/10.1016/j.phymed.2021.153553DOI Listing
June 2021

Stable Eu/Cu-Functionalized Supramolecular Zinc(II) Complexes as Fluorescent Probes for Turn-On and Ratiometric Detection of Hydrogen Sulfide.

ACS Appl Mater Interfaces 2021 May 22;13(17):20371-20379. Epub 2021 Apr 22.

Department of Chemistry, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249-0698, United States.

Fabrication of dual-emitting materials for HS sensing under environmental and biological conditions is currently of great interest. In this work, a new chemically stable metal supramolecular complex [Zn(pda)(HO)]·(HO) (Znpda, pda = 1,10-phenanthroline-2,9-dicarboxylic acid), with accessible uncoordinated carboxylic oxygen sites, is solvothermally synthesized. It can serve as a host in luminescent hybrid composites. By incorporating Eu and Cu in the supramolecular coordination network, we obtained the dual-emitting hybrid material Eu/[email protected], which simultaneously shows intense ligand and weak Eu emissions in HEPES buffer solution. Since HS can easily chelate with Cu and recover the blocked "antenna effect" between the ligand and Eu, Eu/[email protected] possesses both the turn-on and ratiomectric fluorescence response to HS. Accordingly, we designed an IMPLICATION logic gate for HS recognition by employing the fluorescence intensity ratio between the ligand and Eu as the output signal. In addition, Eu/[email protected] shows a fast response (<1 min) and high sensitivity (1.45 μM) to HS over other interfering species in the HEPES buffer solution, highlighting its potential use for HS sensing under environmental and biological conditions.
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http://dx.doi.org/10.1021/acsami.1c04013DOI Listing
May 2021

Clinical and reproductive outcomes of uterine smooth muscle tumor of uncertain malignant potential: a single-center retrospective study.

J Int Med Res 2021 Apr;49(4):3000605211008065

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Objective: To evaluate the clinical outcomes, histopathological features, and obstetric and oncological outcomes of uterine smooth muscle tumor of uncertain malignant potential (STUMP).

Methods: We conducted a single-center, database review of patients with STUMP between January 2001 and December 2015. We investigated the clinical, operative, histopathologic, recurrence, and fertility outcomes of the included cases.

Results: Nineteen patients with STUMP were studied. Three were reclassified as sarcoma after slide review, and 16 patients were finally included in the study. The mean age was 45 years. Ki-67 expression was ≥10% in 25.0% of cases and 30% in the only recurrent case. Recurrence occurred 52 months after a diagnosis of STUMP in a 56-year-old female patient who underwent hysterectomy. Two of six patients who underwent myomectomy had fertility requirements, and both successfully delivered babies without recurrence. Recurrence was not related to mitosis, degree of atypia, or necrosis. There was also no relationship between type of surgery or surgical approach and recurrence.

Conclusions: Patients with STUMP warrant a pathological review process in centers with experience. Fertility-preservation is worth attempting, but young patients must be followed-up closely. Ki-67 might be a valuable marker predicting recurrence.
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http://dx.doi.org/10.1177/03000605211008065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074534PMC
April 2021

Quantifying the Comprehensive Characteristics of Inclusion-Induced Defects Using an Integrated Destructive and Non-Destructive Method.

Materials (Basel) 2021 Mar 17;14(6). Epub 2021 Mar 17.

State Key Laboratory of Advanced Metallurgy, University of Science & Technology Beijing, Beijing 100083, China.

Driven by the continuous improvement of the mechanical properties, especially the fatigue property of the high-strength steels, it is particularly important to characterize the type, size, and distribution of inclusions and the critical inclusions in the steel matrix, as they are decisive for the fatigue life performance. This paper presents an integrated approach for the comprehensive characterization of the inclusions in metals by combining the advantages of destructive methods based on metallography and non-destructive testing methods using ultrasonic detection technology. The position and size of inclusions were obtained by scanning ultrasonic microscope, and the composition and micro-image of inclusions were further analyzed by scanning electron microscope. According to the results obtained by the proposed approach, the distribution laws of oxide inclusions and sulfide inclusions in the samples were statistically analyzed, and then the maximum distribution analysis method was used to predict the maximum inclusions. We compare the predicted size value with the value obtained by the characterization method to establish a certain corresponding relationship. The results show that large defects in metals can be accurately characterized by the proposed method, and the size of inclusions predicted by extreme value analysis is close to that of the scanning electron microscope. The integrated destructive and non-destructive method can reveal the in situ information of inclusions and give the possible relationship between inclusions and process and material properties.
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http://dx.doi.org/10.3390/ma14061475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002838PMC
March 2021

COLGALT2 is overexpressed in ovarian cancer and interacts with PLOD3.

Clin Transl Med 2021 Mar;11(3):e370

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China.

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http://dx.doi.org/10.1002/ctm2.370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989968PMC
March 2021

Regioselective Construction of Chemically Transformed Phosphide-Metal Nanoheterostructures for Enhanced Hydrogen Evolution Catalysis.

Inorg Chem 2021 May 25;60(10):7269-7275. Epub 2021 Mar 25.

Key Laboratory of Advanced Catalytic Materials and Reaction Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009, China.

Engineering nanoheterostructures (NHs) plays a key role in exploring novel or enhanced physicochemical properties of nanocrystals. Despite previously reported synthetic methodologies, selective synthesis of NHs to achieve the anticipated composition and interface is still challenging. Herein, we presented a colloidal strategy for the regioselective construction of typical Ag-CoP NHs with precisely controlled location of Ag nanoparticles (NPs) on unique chemically transformed CoP nanorods (NRs) by simply changing the ratio of different surfactants. As a proof-of-concept study, the constructed heterointerface-dependent hydrogen evolution reaction (HER) catalysis was demonstrated. The multiple Ag NP-tipped CoP NRs exhibited the best HER performance, due to their more exposed active sites and the synergistic effect at the interfaces. Our results open up new avenues in rational design and fabrication of NHs with delicate control over the spatial distribution and interfaces between different components.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00348DOI Listing
May 2021

Enhanced Hardness in Transition-Metal Monocarbides via Optimal Occupancy of Bonding Orbitals.

ACS Appl Mater Interfaces 2021 Mar 18;13(12):14365-14376. Epub 2021 Mar 18.

College of Science, Institute of Functional Materials, and State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, China.

An efficient strategy that can guide the synthesis of materials with superior mechanical properties is important for advanced material/device design. Here, we report a feasible way to enhance hardness in transition-metal monocarbides (TMCs) by optimally filling the bonding orbitals of valence electrons. We demonstrate that the intrinsic hardness of the NaCl- and WC-type TMCs maximizes at valence electron concentrations of about 9 and 10.25 electrons per cell, respectively; any deviation from such optimal values will reduce the hardness. Using the spark plasma sintering technique, a number of WReC ( = 0-0.5) have been successfully synthesized, and powder X-ray diffractions show that they adopt the hexagonal WC-type structure. Subsequent nanoindentation and Vickers hardness measurements corroborate that the newly developed WReC samples ( = 0.1-0.3) are much harder than their parent phase (i.e., WC), marking them as the hardest TMCs for practical applications. Furthermore, the hardness enhancement can be well rationalized by the balanced occupancy of bonding and antibonding states. Our findings not only elucidate the unique hardening mechanism in a large class of TMCs but also offer a guide for the design of other hard and superhard compounds such as borides and nitrides.
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http://dx.doi.org/10.1021/acsami.0c23049DOI Listing
March 2021

Genome-wide association studies provide insights into the genetic determination of fruit traits of pear.

Nat Commun 2021 02 18;12(1):1144. Epub 2021 Feb 18.

Centre of Pear Engineering Technology Research, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Pear is a major fruit tree crop distributed worldwide, yet its breeding is a very time-consuming process. To facilitate molecular breeding and gene identification, here we have performed genome-wide association studies (GWAS) on eleven fruit traits. We identify 37 loci associated with eight fruit quality traits and five loci associated with three fruit phenological traits. Scans for selective sweeps indicate that traits including fruit stone cell content, organic acid and sugar contents might have been under continuous selection during breeding improvement. One candidate gene, PbrSTONE, identified in GWAS, has been functionally verified to be involved in the regulation of stone cell formation, one of the most important fruit quality traits in pear. Our study provides insights into the complex fruit related biology and identifies genes controlling important traits in pear through GWAS, which extends the genetic resources and basis for facilitating molecular breeding in perennial trees.
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http://dx.doi.org/10.1038/s41467-021-21378-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892570PMC
February 2021

Spatio-temporally expressed sorbitol transporters cooperatively regulate sorbitol accumulation in pear fruit.

Plant Sci 2021 Feb 9;303:110787. Epub 2020 Dec 9.

Centre of Pear Engineering Technology Research, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Sorbitol is the primary substrate translocated from source to sink in pear species. Among the many sorbitol transporters (SOTs), some are known to be involved in sorbitol accumulation in fruit; however, their particular roles are unclear. In this study, we examined the transcriptome and metabolome of a variety of pear samples from six time points to identify those SOTs. Similar to previous studies, sorbitol and sucrose differed significantly between the leaf and fruit, and sorbitol was consistently observed at higher concentrations at all time points. Interestingly, we found that sorbitol accumulation in pear fruit was cooperatively mediated by SOT3, SOT6/20, SOT19/21, and SOT22. In particular, the up-regulated SOT6/20 and SOT19/21 in fruit under 1 mg L abscisic acid and 10 mg L indole acetic acid treatments, respectively, resulted in an increased sorbitol concentration. In addition, sorbitol concentration showed positive correlations to fructose and glucose concentrations, indicating a role for sorbitol in the determination of fruit sweetness. Together with the deduced process of sugar biosynthesis, transport, conversion, and accumulation in pear, our study provides a foundation for further research into sugar accumulation processes in pear fruit, contributing to the improvement of fruit quality.
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http://dx.doi.org/10.1016/j.plantsci.2020.110787DOI Listing
February 2021

PLODs are overexpressed in ovarian cancer and are associated with gap junctions via connexin 43.

Lab Invest 2021 May 22;101(5):564-569. Epub 2021 Jan 22.

Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Rd, Shanghai, 200011, PR China.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) play important roles in cancer progression, but their role in ovarian cancer remains elusive. In silico analysis of expression of PLODs in ovarian cancer was performed with reproduction of The Cancer Genome Atlas dataset. PLOD-enriched pathways and related gene(s) were validated by immunohistochemistry (IHC) in 80 ovarian cancer tissue blocks and in vivo xenograft murine models. PLODs (PLOD-1, -2, and -3) were overexpressed in ovarian cancer tissue. Overexpression of individual PLODs showed mutual exclusivity. Each of the three PLODs was differentially expressed between normal and cancer tissue of the ovary. PLOD1 was not prognostic, whereas lower PLOD2 and higher PLOD3 expression were associated with worsened prognosis, respectively. Cases with PLOD overexpression showed enrichment in gap junctions. GJA1 (connexin 43) was significantly overexpressed in cases with PLOD overexpression. IHC in tissue showed the strongest positive correlation between PLOD3 and connexin 43 expression, followed by PLOD2. As per Harmonizome, we selected SKOV3 and CAOV3 cell lines based on constitutive high PLOD1 and PLOD2/PLOD3 expression, respectively for in vitro and in vivo modeling. Only knockdown of PLOD3 was significantly associated with decreased GJA1 expression level in both cell lines. IHC in murine xenograft tumors also showed significantly lower connexin 43 in PLOD3-KD SKOV3 tumors. We conclude that PLODs are generally overexpressed in ovarian cancer and each PLOD may be functionally non-redundant. Association between PLOD3 and gap junctions warrants further investigation.
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http://dx.doi.org/10.1038/s41374-021-00533-5DOI Listing
May 2021

An Efficient Turing-Type Ag Se-CoSe Multi-Interfacial Oxygen-Evolving Electrocatalyst*.

Angew Chem Int Ed Engl 2021 Mar 12;60(12):6553-6560. Epub 2021 Feb 12.

Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, China.

Although the Turing structures, or stationary reaction-diffusion patterns, have received increasing attention in biology and chemistry, making such unusual patterns on inorganic solids is fundamentally challenging. We report a simple cation exchange approach to produce Turing-type Ag Se on CoSe nanobelts relied on diffusion-driven instability. The resultant Turing-type Ag Se-CoSe material is highly effective to catalyze the oxygen evolution reaction (OER) in alkaline electrolytes with an 84.5 % anodic energy efficiency. Electrochemical measurements show that the intrinsic OER activity correlates linearly with the length of Ag Se-CoSe interfaces, determining that such Turing-type interfaces are more active sites for OER. Combing X-ray absorption and computational simulations, we ascribe the excellent OER performance to the optimized adsorption energies for critical oxygen-containing intermediates at the unconventional interfaces.
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http://dx.doi.org/10.1002/anie.202017016DOI Listing
March 2021

Multiomics analyses unveil the involvement of microRNAs in pear fruit senescence under high- or low-temperature conditions.

Hortic Res 2020 Dec 1;7(1):196. Epub 2020 Dec 1.

Centre of Pear Engineering Technology Research, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China.

Senescence leads to declines in fruit quality and shortening of shelf life. It is known that low temperatures (LTs) efficiently delay fruit senescence and that high temperatures (HTs) accelerate senescence. However, the molecular mechanism by which temperature affects senescence is unclear. Herein, through multiomics analyses of fruits subjected to postharvest HT, LT, and room temperature treatments, a total of 56 metabolic compounds and 700 mRNAs were identified to be associated with fruit senescence under HT or LT conditions. These compounds could be divided into antisenescent (I→III) and prosenescent (IV→VI) types. HT affected the expression of 202 mRNAs to enhance the biosynthesis of prosenescent compounds of types V and VI and to inhibit the accumulation of antisenescent compounds of types II and III. LT affected the expression of 530 mRNAs to promote the accumulation of antisenescent compounds of types I and II and to impede the biosynthesis of prosenescent compounds of types IV and V. Moreover, 16 microRNAs were isolated in response to HT or LT conditions and interacted with the mRNAs associated with fruit senescence under HT or LT conditions. Transient transformation of pear fruit showed that one of these microRNAs, Novel_188, can mediate fruit senescence by interacting with its target Pbr027651.1. Thus, both HT and LT conditions can affect fruit senescence by affecting microRNA-mRNA interactions, but the molecular networks are different in pear fruit.
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http://dx.doi.org/10.1038/s41438-020-00420-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705739PMC
December 2020

Organoid culture system for patient-derived lung metastatic osteosarcoma.

Med Oncol 2020 Oct 20;37(11):105. Epub 2020 Oct 20.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Research Center of Biliary Tract Disease, Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Osteosarcoma (OS) is the most common primary bone malignancy with high rates of recurrence and metastasis. OS often spreads to lungs, an optimized model for studying lung metastatic OS cells may help develop potential therapies for patients with lung metastasis. Here we firstly report an organoid culture system for lung metastatic OS tissues. We provided a fully described formula that was required for establishing lung metastatic OS organoids (OSOs). Using this protocol, the lung OSOs were able to be maintained and serially propagated for at least six months; the OSOs can also be generated from cryopreserved patient samples without damaging the morphology. The patient-derived lung OSOs retained the cellular morphology and expression of OS markers (Vimentin and Sox9) that recapitulate the histological features of the human OS. The microenvironment of primary lung metastatic OSOs preserved a similar T cell distribution with the human lung OS lesions; this provided a possible condition to explore how OS cells may react to immunotherapy. OSOs established from this protocol can be further utilized for studying various aspects of OS biology (e.g., tumorigenesis and drug screen/discovery) for precision medicine.
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http://dx.doi.org/10.1007/s12032-020-01429-yDOI Listing
October 2020

Bimetallic nickel-molybdenum/tungsten nanoalloys for high-efficiency hydrogen oxidation catalysis in alkaline electrolytes.

Nat Commun 2020 Sep 22;11(1):4789. Epub 2020 Sep 22.

Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Institute of Energy, Hefei Comprehensive National Science Center, CAS Center for Excellence in Nanoscience, Department of Chemistry, Institute of Biomimetic Materials and Chemistry, University of Science and Technology of China, 230026, Hefei, China.

Hydroxide exchange membrane fuel cells offer possibility of adopting platinum-group-metal-free catalysts to negotiate sluggish oxygen reduction reaction. Unfortunately, the ultrafast hydrogen oxidation reaction (HOR) on platinum decreases at least two orders of magnitude by switching the electrolytes from acid to base, causing high platinum-group-metal loadings. Here we show that a nickel-molybdenum nanoalloy with tetragonal MoNi phase can catalyze the HOR efficiently in alkaline electrolytes. The catalyst exhibits a high apparent exchange current density of 3.41 milliamperes per square centimeter and operates very stable, which is 1.4 times higher than that of state-of-the-art Pt/C catalyst. With this catalyst, we further demonstrate the capability to tolerate carbon monoxide poisoning. Marked HOR activity was also observed on similarly designed WNi catalyst. We attribute this remarkable HOR reactivity to an alloy effect that enables optimum adsorption of hydrogen on nickel and hydroxyl on molybdenum (tungsten), which synergistically promotes the Volmer reaction.
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http://dx.doi.org/10.1038/s41467-020-18585-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508880PMC
September 2020

Investigation on the Interaction between Cellulosic Paper and Organic Acids Based on Molecular Dynamics.

Molecules 2020 Aug 28;25(17). Epub 2020 Aug 28.

Equipment Status Evaluation Center, State Grid Shandong Electric Power Research Institute, Jinan 250002, China.

Organic acid is an important factor that accelerates the aging of cellulosic insulation materials. In this study, the interactions between cellulose and five acids, representative of what may be found in an aging transformer, were studied using molecular dynamics. The adsorption process of the five acids onto the surface of crystalline cellulose shows that the three low molecular acids are more readily adsorbed onto cellulose than the two high molecular acids. The deformation and adsorption energies of the acids all increase with an increase in molecular weight when they are stably interacting with cellulose. However, the differences between adsorption energies and deformation energies are positive for the three low molecular acids, whereas they are negative for the two high molecular acids. This indicates that the attachments onto cellulose of low molecular acids are considerably more stabilized than those of the high molecular acids. This is consistent with the experimental results. Furthermore, based on the calculated solubility parameters of acids, the experimental result that the three low molecular acids are to a large degree absorbed onto the cellulose, whereas the two high molecular acids remain in the oil, was theoretically elucidated using the theory of similarity and intermiscibility.
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http://dx.doi.org/10.3390/molecules25173938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504618PMC
August 2020

PbrPOE21 inhibits pear pollen tube growth in vitro by altering apical reactive oxygen species content.

Planta 2020 Sep 1;252(3):43. Epub 2020 Sep 1.

College of Horticulture, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China.

Main Conclusion: Genome-wide identification, tissue-specific expression analysis and functional characterization of selected genes containing the pear Pollen Olea europaea I domain reveal their roles in pollen tube growth. Genes containing the Pollen Olea europaea I (POE) domain play crucial roles in diverse growth and developmental processes. Nevertheless, the specific functions of POE family members in progression of pollen tube growth (PTG) remain uncharacterized. We identified 45 PbrPOE genes in the pear (Pyrus bretschneideri) genome, clustered into seven subclasses. PbrPOE genes contained 1 to 11 exons and 0 to 10 introns, with exon/intron structure mostly conserved within each subclass. Whole-genome duplication has mainly contributed to the duplication pattern of PbrPOE genes in pear. Expression profiles of 45 PbrPOE genes in 12 different pear tissues revealed that six PbrPOE genes (PbrPOE6, 12, 21, 29, 35 and 41) of subclass B were highly expressed during the growth of the pear pollen tube in vitro. PbrPOE21 was selected for further functional analysis on the basis of its high and differential expression pattern in pollen. Antisense oligodeoxynucleotide assays demonstrated that PTG was augmented in vitro when PbrPOE21 expression was significantly inhibited. Moreover, pollen tube length in vitro was reduced when PbrPOE21 was transitorily over-expressed using particle bombardment technology. Exogenous PbrPOE21 recombinant protein inhibited PTG in vitro at an optimum concentration of 1.8 µM. PbrPOE21 also affected reactive oxygen species content in the pear pollen tube apex. We suggest that PbrPOE21 inhibits PTG in vitro by altering apical reactive oxygen species content.
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http://dx.doi.org/10.1007/s00425-020-03446-7DOI Listing
September 2020

Therapeutic Effects of SRT2104 on Lung Injury in Rats with Emphysema via Reduction of Type II Alveolar Epithelial Cell Senescence.

COPD 2020 08 28;17(4):444-451. Epub 2020 Jul 28.

Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), Jiaxing, Zhejiang, People's Republic of China.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent and severe diseases worldwide with high societal and health care costs. The pathogenesis of COPD is very complicated, and no curative treatment is available. Cellular senescence promotes the development of COPD. Type II alveolar epithelial cells (AECII) play a momentous role in lung tissue repair and maintenance of alveolar homeostasis. Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to chronic inflammation and oxidative stress, regulates many pathophysiological changes including stress resistance, apoptosis, inflammation, and cellular senescence. This study aimed to investigate whether the pharmacological SIRT1 activator SRT2104 protects against AECII senescence in rats with emphysema. Our findings confirmed that SRT2104 administration reduced the pathological characteristics of emphysema and improved lung function parameters, including pulmonary resistance, pulmonary dynamic compliance, and peak expiratory flow. Moreover, SRT2104 treatment upregulated the expression of surfactant proteins A and C, SIRT1, and forkhead box O 3a (FoxO3a), decreased senescence-associated-β-galactosidase (SA-β-gal) activity, increased SIRT1 deacetylase activity, and downregulated the levels of p53 and p21. Therefore, SRT2104 administration protected against AECII senescence in rats with emphysema via SIRT1/FoxO3a and SIRT1/p53 signaling pathways and may provide a novel potential therapeutic strategy for COPD.
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http://dx.doi.org/10.1080/15412555.2020.1797657DOI Listing
August 2020

Effects of Montmorillonite on Growth Performance, Serum Biochemistry and Oxidative Stress of Red-Crowned Crane () Fed Mycotoxin-Contaminated Feed.

Curr Drug Metab 2020 ;21(8):626-632

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Background: The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redcrowned crane's regular diets in China.

Objective: This experiment was conducted to investigate the protective effects of mycotoxin binder montmorillonite (Mont) on growth performance, serum biochemistry and oxidative stress parameters of the red-crowned crane.

Methods: 16 red-crowned cranes were divided into four groups and fed one of the following diets; a selected diet, regular diet, or the selected diet or regular diet with 0.5% montmorillonite added to the diets. The cranes' parameters of performance, hematology, serum biochemistry and serum oxidative stress were measured.

Results: Consuming regular diets decreased the average daily feed intake (ADFI), levels of haemoglobin (Hb), platelet count (PLT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), but increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK) and lactate dehydrogenase (LDH). The supplementation of 0.5% Mont provided protection for the red-crowned crane in terms of feed intake, serum biochemistry and oxidative stress. Moreover, Mont supplementation had no adverse effect on the health of red-crowned crane.

Conclusions: Taken together, these findings suggested that the addition of dietary Mont is effective in improving the health of red-crowned crane.
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http://dx.doi.org/10.2174/1389200221666200726221126DOI Listing
January 2020

Chemical characteristics of road dust PM fraction in oasis cities at the margin of Tarim Basin.

J Environ Sci (China) 2020 Sep 8;95:217-224. Epub 2020 May 8.

College of Water Sciences, Beijing Normal University, Beijing 100875, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

In order to understand the compositions characteristics of particulate matter with aerodynamic diameter less than 2.5 μm (PM) fraction in road dust (RD) of oasis cities on the edge of Tarim Basin, 30 road dust (RD) samples were collected in Kashi, Cele, and Yutian in the spring, 2018, and RD was collected using the resuspension approach. Eight water-soluble ions, 39 trace elements and 8 fractions of carbon-containing species in PM were analyzed. Ca and Ca were the most abundant ions and elements in RD (7.1% and 9.5%). Cl in RD was affected not only by attributed to saline-alkali soils in oasis cities of the Tarim Basin and dust from Taklimakan Desert but also by human activities. Moreover, the organic carbon/elemental carbon (OC/EC) ratio indicated that carbon components in RD in Cele town mainly come from fossil fuel combustion, while those in Yutian and Kashi mainly come from biomass combustion. It is noteworthy that high Ca in RD was seriously affected by anthropogenic emissions, and high Na and K contents in RD could be derived from soil and desert dust. It was estimated that Cd, Tl, Sn and Cr were emitted from anthropogenic emissions using the enrichment factor. The coefficients of divergence (COD) result indicated that the influence of local emission on road dust emission is greater than that of long-distance transmission. This study is the first time to comprehensively analyze the chemical characteristics of road dust in oasis cities, and the results provides the sources of road dust at the margin of Tarim Basin.
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http://dx.doi.org/10.1016/j.jes.2020.03.030DOI Listing
September 2020

MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function.

Cell Commun Signal 2020 07 9;18(1):107. Epub 2020 Jul 9.

Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, Hubei, 430081, PR China.

Background: Foxp3CD4 regulatory T cells (Treg) constitutes a key event in autoimmune diseases. STAT5b is the critical link between the IL-2/15 and FOXP3, the master regulator of Treg cells.

Methods: The CD3T cell and Foxp3CD4 regulatory T cells were overexpressioned or knockdown MKL-1 and STAT5a and tested for Treg cell development and function. Direct interaction of MKL-1 and STAT5a were analyzed by coimmunoprecipitation assays, Luciferase assay, Immunofluoresence Staining and Yeast two-hybrid screening. The effect of MKL-1 and STAT5a on the Treg genes expression was analyzed by qPCR and western blotting and Flow cytometry.

Results: However, the molecular mechanisms mediating STAT5b-dependent Treg genes expression and Treg cell phenotype and function in autoimmune diseases are not well defined. Here, we report that the MKL-1 is a coactivator for the major Treg genes transcription factor STAT5b, which is required for human Treg cell phenotype and function. The N terminus of STAT5b, which contains a basic coiled-coil protein-protein interaction domain, binds the C-terminal activation domain of MKL-1 and enhances MKL-1 mediated transcriptional activation of Treg-specific, CArG containing promoters, including the Treg-specific genes Foxp3. Suppression of endogenous STAT5b expression by specific small interfering RNA attenuates MKL-1 transcriptional activation in cultured human cells. The STAT5b-MKL-1 interaction identifies a role of Treg-specific gene regulation and regulated mouse Treg cell development and function and suggests a possible mechanism for the protective effects of autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP).

Conclusions: Our studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00574-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350762PMC
July 2020

Obesity influences the outcomes of anti-IgE (omalizumab) therapy of asthma.

Clin Exp Allergy 2020 10 13;50(10):1196-1199. Epub 2020 Jul 13.

Department of Immunology, Mayo Clinic, Scottsdale, Arizona, USA.

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http://dx.doi.org/10.1111/cea.13696DOI Listing
October 2020

Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer's disease through a network pharmacology approach.

BMC Complement Med Ther 2020 May 25;20(1):157. Epub 2020 May 25.

Department of Science & Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.

Background: Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach.

Methods: The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool.

Results: A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and β-sitosterol were obtained from the analysis of the key targets.

Conclusions: Ursolic acid, anethole and β-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.
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http://dx.doi.org/10.1186/s12906-020-02951-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249309PMC
May 2020

Therapeutic efficacy of two surgical methods on the secondary hyperparathyroidism.

Gland Surg 2020 Apr;9(2):321-328

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.

Background: This study aimed to investigate the clinical efficacy of two surgical methods on hyperparathyroidism secondary to uremia and summarize the advantages and disadvantages of both methods.

Methods: Uremic patients who received parathyroidectomy (PTX) in the last 3 years were divided into two groups according to the surgical methods used [subtotal parathyroidectomy (SPTX) group and total parathyroidectomy + autologous implantation (TPTX + AT) group]. TPTX was performed if less than 4 glands were found during surgery. The changes of various indexes after operation, and calculate the success rate and recurrence rate of patients were observed. The serum biochemical parameters were routinely monitored, the success rate, postoperative complications and recurrence were recorded. The patients were followed up.

Results: There were 20 patients in the SPTX group and 12 in the TPTX + AT group. The success rate of surgery was 85% and 91.7% in the SPTX group and TPTX + AT group, respectively, among 32 patients included for final analysis. The mean PTH and postoperative ALP in the TPTX + AT group were slightly lower than in the SPTX group, except for the PTH levels at 6 months after surgery (P<0.05). The incidence of postoperative hypocalcemia was 100% in both groups. The incidence of wound infection in the two groups was 0% and 16.7% in the SPTX group and TPTX + AT group, respectively. The mean calcium supplementation in the TPTX + AT group was significantly more than in the SPTX group within 1 year after surgery. The mean postoperative bone mineral density in the SPTX group was significantly higher than in the TPTX + AT group. The time to postoperative remission of bone pain and muscle weakness was markedly shorter in the SPTX group than in the TPTX + AT group. The post-operative quality of life (QOL) in the SPTX group was significantly better than in the TPTX + AT group.

Conclusions: These findings suggest that SPTX achieves a better short-term efficacy, but TPTX + AT has a better long-term efficacy. Therefore, the selection of surgical method for PTX may be based on the age, estimated survival time and possibility of kidney transplantation.
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http://dx.doi.org/10.21037/gs.2020.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225472PMC
April 2020

p85β regulates autophagic degradation of AXL to activate oncogenic signaling.

Nat Commun 2020 05 8;11(1):2291. Epub 2020 May 8.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

PIK3R2 encodes the p85β regulatory subunit of phosphatidylinositol 3-kinase and is frequently amplified in cancers. The signaling mechanism and therapeutic implication of p85β are poorly understood. Here we report that p85β upregulates the protein level of the receptor tyrosine kinase AXL to induce oncogenic signaling in ovarian cancer. p85β activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, which are all abolished upon inhibition of AXL. At the molecular level, p85β alters the phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate the selective regulation of AXL by p85β, thereby disrupting the autophagic degradation of the AXL protein. Therapeutically, p85β expression renders ovarian cancer cells vulnerable to inhibitors of AXL, p110, or PDK1. Conversely, p85β-depleted cells are less sensitive to these inhibitors. Together, our findings provide a rationale for pharmacological blockade of the AXL signaling axis in PIK3R2-amplified ovarian cancer.
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http://dx.doi.org/10.1038/s41467-020-16061-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210311PMC
May 2020