Publications by authors named "Jianjun Zhang"

748 Publications

Lung cancer models reveal SARS-CoV-2-induced EMT contributes to COVID-19 pathophysiology.

J Thorac Oncol 2021 Jul 15. Epub 2021 Jul 15.

Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

COVID-19 is an infectious disease caused by SARS-CoV-2, which enters host cells via the cell surface proteins ACE2 and TMPRSS2. Using a variety of normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2. We find that ACE2 expression is restricted to a select population of epithelial cells. Notably, infection with SARS-CoV-2 in cancer cell lines, bronchial organoids, and patient nasal epithelium, induces metabolic and transcriptional changes consistent with epithelial to mesenchymal transition (EMT), including upregulation of ZEB1 and AXL, resulting in an increased EMT score. Additionally, a transcriptional loss of genes associated with tight junction function occurs with SARS-CoV-2 infection. The SARS-CoV-2 receptor, ACE2, is repressed by EMT via TGFbeta, ZEB1 overexpression and onset of EGFR TKI inhibitor resistance. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state, associated with a loss of tight junction components with acute respiratory distress syndrome-protective effects. AXL-inhibition and ZEB1-reduction, as with bemcentinib, offers a potential strategy to reverse this effect. These observations highlight the utility of aerodigestive and, especially, lung cancer model systems in exploring the pathogenesis of SARS-CoV-2 and other respiratory viruses, and offer important insights into the potential mechanisms underlying the morbidity and mortality of COVID-19 in healthy patients and cancer patients alike.
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http://dx.doi.org/10.1016/j.jtho.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282443PMC
July 2021

Development of colloidal gold-based test strip for rapid detection of serotype 4 fowl adenovirus.

J Virol Methods 2021 Jul 7;296:114231. Epub 2021 Jul 7.

Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, 225009, China. Electronic address:

The outbreaks of hepatitis-hydropericardium syndrome (HPS) caused by serotype 4 fowl adenovirus (FAdV-4) have spread from broilers to laying hens, breeders, geese and Cherry Valley duck, resulting in high economic losses to the poultry industry globally. In this study, a rapid colloidal gold test strip for detection of FAdV-4 was developed by using two monoclonal antibodies (mAbs) against the Fiber-2 of FAdV-4. Specificity analysis revealed that the test strip only reacted with FAdV-4, but not with other pathogens including different serotypes of fowl adenovirus and other avian pathogens tested. The limit of the detection (LOD) of the strip could reach as low as 0.1 μg/0.1 mL of GST-Fiber-2 protein and 1 × 10 TCID/0.1 mL of FAdV-4, respectively. Moreover, the test strip could be efficiently applied in detecting tissue samples from diseased chickens with HPS. Comparison analysis further revealed that the test strip showed good compatibility with PCR assay for detection of virus isolates and clinical samples. In conclusion, our test strip provides an efficient on-site diagnostic method in a quick and convenient manner for detection of FAdV-4, especially in resource-limited areas.
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http://dx.doi.org/10.1016/j.jviromet.2021.114231DOI Listing
July 2021

Dimensional structure regulation of organic-inorganic hybrid perovskite and its application in thin film transistors.

Nanotechnology 2021 Jul 7;32(39). Epub 2021 Jul 7.

Institute of Photoelectronic Thin Film Devices and Technology, Key Laboratory of Photoelectronic Thin Film Devices and Technology of Tianjin, Tianjin, People's Republic of China.

The effects of dimensional structure on the properties of lead iodide perovskite (CHNH)(CHNH)PbIwere investigated. Furthermore, perovskite thin films with different dimensionalities were applied as the channel layer of thin film transistors (TFT). The electrical performance and stability of TFT devices were significantly improved through the regulation of dimensional microstructure of the perovskites. As a result, the quasi-2D ( = 6) perovskite TFTs achieved a field-effect mobility () of 3.90 cmVs, with 10on-off current ratio and -1.85 V threshold voltage, which can be maintained well after 4 days without degradation at 30% ambient humidity. Moreover, the electrical performance of the TFTs based on Pure-2D and Quasi-2D perovskite also exhibited a good bias stability.
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http://dx.doi.org/10.1088/1361-6528/ac0d1fDOI Listing
July 2021

Puerarin-Na Chelate Hydrate Simultaneously Improves Dissolution and Mechanical Behavior.

Mol Pharm 2021 Jul 18;18(7):2507-2520. Epub 2021 Jun 18.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.

Puerarin monohydrate (PUEM), as the commercial solid form of the natural anti-hypertension drug puerarin (PUE), has low solubility, poor flowability, and mechanical properties. In this study, a novel solid form as PUE-Na chelate hydrate was prepared by a reactive crystallization method. Crystal structure analysis demonstrated that PUE-Na contains PUE, Na, and water in a molar ratio of 1:1:7. It crystallizes in the monoclinic space group 2, and Na is linked with PUE and four water molecules through Na ← O coordination bonds. Another three crystal water molecules occupy channels along the crystallographic -axis. Observing along the -axis, the crystal structure features a distinct tubular helix and a DNA-like twisted helix. The complexation between Na and PUE in aqueous solution was confirmed by the Na selective electrode, indicating that PUE-Na chelate hydrate belongs to a type of chelate rather than organic metal salt. Compared with PUEM, PUE-Na exhibited a superior dissolution rate (i.e., ∼38-fold increase in water) owing to its lower solvation free energy and clear-enriched exposed polar groups. Moreover, PUE-Na enhanced the tabletability and flowability of PUEM, attributing to its better elastoplastic deformation and lower-friction crystal habit. The unique PUE-Na chelate hydrate with significantly enhanced pharmaceutical properties is a very promising candidate for future product development of PUE.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00005DOI Listing
July 2021

Expression profiles and functional analysis of plasma tRNA-derived small RNAs in children with fulminant myocarditis.

Epigenomics 2021 Jul 11;13(13):1057-1075. Epub 2021 Jun 11.

Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, PR China.

Fulminant myocarditis (FM) has neither validated biomarkers nor well-established therapy. Roles of tRNA-derived small RNAs (tsRNAs) in FM remain unknown. Small RNA sequencing was conducted in plasma from children with FM during acute and convalescent phase and matched healthy volunteers. Data were validated by quantitative real-time PCR in larger sample-sized groups and . Functional analysis was performed to explore the roles. tiRNA-Gln-TTG-001 was overexpressed in children with FM during acute phase, and the generation and extracellular release of tiRNA-Gln-TTG-001 were higher after myocarditis-mimicked activity . Several pathways might participate in the pathogenesis of FM. tsRNAs may play an important role in FM, and tiRNA-Gln-TTG-001 might represent a novel and promising biomarker and therapeutic target.
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http://dx.doi.org/10.2217/epi-2021-0109DOI Listing
July 2021

The Efficacy and Medium to Long-Term Follow-Up of Transcatheter Retrograde Closure of Perimembranous Ventricular Septal Defects via the Femoral Artery With Amplatzer Duct Occluder II in Children.

Front Pediatr 2021 25;9:571407. Epub 2021 May 25.

Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

The aim of this study was to assess the efficacy and safety of transcatheter retrograde closure of perimembranous ventricular septal defect (pmVSD) via the femoral artery with an Amplatzer Duct Occluder II (ADO II) in children. The clinical and follow-up data of 102 children who had successfully undergone transcatheter retrograde closure of pmVSD via the femoral artery with Amplatzer Duct Occluder II (ADO II) from February 2012 to June 2019 in our center were retrospectively reviewed. In 102 of 103 patients, the defects were successfully closed (99.0%). The average age was 4.03 ± 1.84 years and the mean weight was 17.50 ± 5.58 kg. The mean diameter of the defects was 2.58 ± 0.63 mm. Hundred of the occluders had a waist length of 4 mm. The complete closure rate was 89.2% 24 h after the procedure and 98% at the last follow-up. The follow-up period ranged from 6 to 92 months, with a median of 36 months. One child developed new mild aortic regurgitation (AR), and 9 patients developed new mild tricuspid regurgitation (TR). During follow-up, TR disappeared in 5 patients and decreased in 4 patients, and AR relieved in one patient. One patient developed intermittent complete left bundle branch block 4 days after the procedure and recovered sinus rhythm 2 days later. No serious complications occurred. Transcatheter retrograde closure of pmVSD via the femoral artery with ADO II in children is safe, feasible, and effective in selected patients.
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http://dx.doi.org/10.3389/fped.2021.571407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185017PMC
May 2021

Long noncoding RNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5.

Mol Ther 2021 Jun 7. Epub 2021 Jun 7.

Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, PR China. Electronic address:

Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. Vomeronasal type-1 receptor 5 (VN1R5) was identified as a cisplatin resistance-related protein and was highly expressed in cisplatin-resistant HNSCC cells and tissues. The long noncoding RNA (lncRNA) lnc-POP1-1 was confirmed to be a downstream target induced by VN1R5. VN1R5 transcriptionally regulated lnc-POP1-1 expression by activating the specificity protein 1 (Sp1) transcription factor via the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. VN1R5 promoted cisplatin resistance in HNSCC cells in a lnc-POP1-1-dependent manner. Mechanistically, lnc-POP1-1 bound to the Minichromosome Maintenance Deficient 5 (MCM5) protein directly and decelerated MCM5 degradation by inhibiting ubiquitination of the MCM5 protein, which facilitated the repair of DNA damage caused by cisplatin. In summary, we identified the cisplatin resistance-related protein VN1R5 and its downstream target lnc-POP1-1. Upon upregulation by VN1R5, lnc-POP1-1 promotes DNA repair in HNSCC cells through interaction with MCM5 and deceleration of its degradation.
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http://dx.doi.org/10.1016/j.ymthe.2021.06.006DOI Listing
June 2021

Pediatric living-donor liver transplantation using right posterior segment grafts.

BMC Gastroenterol 2021 Jun 6;21(1):249. Epub 2021 Jun 6.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160 Pujian Road, Pudong New District, Shanghai, 200127, China.

Background: The right posterior segment (RPS) graft was introduced to overcome graft size discrepancy in living donor liver transplantation (LDLT). However, it was very rarely used in pediatric patients. Here we presented 4 pediatric LDLT cases receiving RPS graft between January 2015 and April 2020 in our center. A total of 1868 LDLT procedures were performed in this period.

Methods: Recipients included 1 boy and 3 girls with a median age of 45 months (range from 40 to 93 months). They were diagnosed with progressive familial intrahepatic cholestasis, propionic academia, ornithine transcarbamylase and biliary atresia, respectively. Four donors were all mothers with a median age of 32.5 years (31-38 years). Computer tomography angiography indicated posterior right branches branched off separately from main portal veins (type III variation). Three of these donor livers had 1 orifice of right hepatic veins (RHV). In the remaining 1 donor liver, the RHV showed 3 orifices and an outflow patch plastic was performed. Inferior right hepatic veins weren't found in four donor grafts. The median graft weight was 397.5 g (352-461 g) and the median graft-to-recipient weight ratio was 2.38% (1.44-2.80%).

Results: Postoperative complications occurred in neither donors nor recipients. Within the median follow-up duration of 29 months (14-64 months), four children are all alive with normal liver function.

Conclusion: In summary, for older children weighed more than 15 kg with donors' variation of type III portal veins, the use of RPS grafts could be a feasible and favorable option.
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http://dx.doi.org/10.1186/s12876-021-01835-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183075PMC
June 2021

Targeting P2RX1 alleviates renal ischemia/reperfusion injury by preserving mitochondrial dynamics.

Pharmacol Res 2021 Jun 6;170:105712. Epub 2021 Jun 6.

Department of Liver Surgery, Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address:

Renal ischemia/reperfusion injury (IRI) is the major cause of acute kidney injury. However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we performed RNA sequencing to systematically compare the transcriptome differences between IR injured kidneys and sham kidneys. We observed that mitochondrial dynamics was destructed in renal IRI. Expression of mitochondrial fusion-associated genes was reduced, whereas expression of mitochondrial fission-related genes was increased in renal IRI, and these findings were further confirmed by mitochondrial morphological observations. By screening 19 purinergic receptors, we noticed that P2RX1 expression was markedly upregulated in renal IRI. RNA sequencing and mitochondrial morphological observations revealed that mitochondrial dynamics was preserved in P2RX1 genetic knockout (P2rx1) mice. Neutrophil extracellular traps (NETs) were reported to be essential for tissue injury in renal IRI, but the detailed mechanism remained unclear. In the present study, we found that P2RX1 favored the formation of neutrophil extracellular traps (NETs) in IRI, and NETs was essential for the impairment of mitochondrial dynamics. Mechanistically, P2RX1-involved metabolic interaction between platelets and neutrophils supported NETs formation. Activation of P2RX1 promoted platelets ATP release, which subsequently contributed to neutrophil glycolytic metabolism and NETs generation.
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http://dx.doi.org/10.1016/j.phrs.2021.105712DOI Listing
June 2021

NBR2 promotes the proliferation of glioma cells via inhibiting p15 expression.

J BUON 2021 Mar-Apr;26(2):388-394

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.

Purpose: The purpose of this study was to investigate whether NBR2 can affect the proliferation of glioma cells by inhibiting the expression of p15, so as to promote the occurrence and development of glioma.

Methods: The expression of NBR2 in 44 glioma tissue specimens was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of NBR2 on cell viability, cell colony formation as well as cell migration and invasion abilities were examined by cell counting kit-8 (CCK-8) assay, plate cloning assay and Transwell assay. p15 protein was detected using Western blot. After simultaneous knockdown of NBR2 and p15, qRT-PCR, CCK-8, and plate cloning experiments were adopted to analyze p15 gene level, cell viability and proliferation ability, respectively.

Results: NBR2 was highly expressed in glioma tissues, and the level in stage III/IV glioma tissues was conspicuously higher than that in stage I/II. The overall survival rate of glioma patients with high NBR2 level was conspicuously lower than those with low NBR2 expression. Clinical data analysis revealed that NBR2 expression was correlated with the WHO stage of clinical patients. After knockdown of NBR2, it was found that NBR2 level, cell viability, cell proliferation ability as well as migration and invasion abilities were all conspicuously reduced. In addition, the protein level of p15 was significantly increased after NBR2 was inhibited. Meanwhile, knockout of p15 could reverse the inhibitory effect of NBR2 on glioma cell proliferation.

Conclusions: The highly-expressed NBR2 inhibits the expression of p15, thus promoting the proliferation of glioma cells.
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June 2021

Transcatheter Device Closure of Perimembranous and Intracristal Ventricular Septal Defects in Children: Medium- and Long-Term Results.

J Am Heart Assoc 2021 Jun 17;10(11):e020417. Epub 2021 May 17.

Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China.

Background In children, the practice of transcatheter closure of intracristal ventricular septal defect (icVSD) has been limited. Currently, there is a lack of comparison between device closure of perimembranous ventricular septal defect (pmVSD) and icVSD, and long-term clinical outcomes are rare. Methods and Results This study included a total of 633 children (39 with icVSD and 594 with pmVSD), aged 18 months to 16 years, who underwent transcatheter closure of ventricular septal defect between January 2014 and December 2018. All patients were followed up until September 2020, with a median follow-up of 46 months in the pmVSD group and 52 months in the icVSD group. The procedural success rate was 96.3% and 84.6% in pmVSD and icVSD groups, respectively (=0.002). The median of age, weight, procedure time, fluoroscopic time, and radiation dose were greater in the icVSD group compared with the pmVSD group. More eccentric ventricular septal defect occluders were used in the icVSD group. Most adverse events were minor without any intervention, with cardiac rhythm/conduction abnormalities being the most common. In the pmVSD group, 2 patients experienced complete atrioventricular block, with one implanting a permanent pacemaker and the other dying of cardiac arrest secondary to reversible complete atrioventricular block 40 days postprocedure. Complete left bundle-branch block occurred in 14 patients, and 12 cases were transient. In the icVSD group, no complete atrioventricular block or death occurred, and one patient developed transient complete left bundle-branch block. Conclusions In selected patients, transcatheter device closure of pmVSD and icVSD can be performed safely and successfully, with excellent medium- and long-term results in children.
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http://dx.doi.org/10.1161/JAHA.120.020417DOI Listing
June 2021

Increased cocaine motivation in tree shrews is modulated by striatal dopamine D1 receptor-mediated upregulation of Ca 1.2.

Addict Biol 2021 May 13:e13053. Epub 2021 May 13.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

The progressively increased motivation for cocaine during abstinence is closely associated with the dysfunction of dopamine (DA) system. As DA receptors also dynamically regulate L-type calcium channels (LTCCs), in this study we examined how DA receptors (D1R or D2R) and LTCCs (Ca 1.2 or Ca 1.3) exert their influences on cocaine-seeking in a tree shrew (Tupaia belangeri chinensis) model. First, we demonstrated the 'incubation' effect by showing tree shrews exhibited a significantly higher seeking behaviour on withdrawal day (WD) 45 than on WD1. Then, we confirmed that longer abstinence period induced higher D1R expression in the nucleus accumbens (NAc). Next, we showed that LTCCs in the NAc participated in drug seeking. Moreover, Ca 1.2 expression in the NAc was increased on WD45, and disruption of the Ca 1.2 inhibited drug seeking. Finally, we found that D1R antagonist blocked the increase of Ca 1.2 on drug-seeking test. Collectively, these findings suggest that D1R-mediated upregulation of Ca 1.2 is involved in the incubation of cocaine craving.
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http://dx.doi.org/10.1111/adb.13053DOI Listing
May 2021

Targeting epigenetic modulation of cholesterol synthesis as a therapeutic strategy for head and neck squamous cell carcinoma.

Cell Death Dis 2021 May 13;12(5):482. Epub 2021 May 13.

Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.

The histone methyltransferase EZH2 silences gene expression via H3 lysine 27 trimethylation and has been recognized as an important antitumour therapeutic target. However, the clinical application of existing EZH2 inhibitors is not satisfactory for the treatment of solid tumours. To discover novel strategies against head and neck squamous cell carcinoma (HNSCC), we performed genomics, metabolomics and RNA omics studies in HNSCC cells treated with EZH2 inhibitors. It was found that EZH2 inhibitors strongly induced the expression of genes in cholesterol synthesis. Through extensive drug screening we found that inhibition of squalene epoxidase (a key enzyme of endogenous cholesterol synthesis) synergistically increased the squalene content and enhanced the sensitivity of HNSCC cells to EZH2 inhibitors. Our findings provide an experimental and theoretical basis for the development of new combinations of EZH2 inhibitors to treat HNSCC.
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http://dx.doi.org/10.1038/s41419-021-03760-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119982PMC
May 2021

Nanoscale Phase Separation in Ternary Organic Solar Cells Based on PTB7:PCBM:ICBA.

J Nanosci Nanotechnol 2021 Nov;21(11):5749-5755

College of Electronic Information and Optical Engineering, Nan kai University, Tianjin 300071, People's Republic of China.

As a fullerene derivative, ICBA is widely used in the ternary organic solar cells (TOSCs) to increase the open circuit voltage (V) of the devices. Unfortunately, most of the literature shows that ICBA will lead to a reduction in the short-circuit current density (J) and fill factor (FF). In this work, ICBA is added to the PTB7:PCBM binary system to form the ternary system, which is composed of one donor and two fullerene acceptors. Surprisingly, the addition of ICBA does not immediately lead to a decrease in J and FF. In fact, the appropriate weight ratio of ICBA in fullerenes can simultaneously increase the V, J, and FF of the TOSCs. The synergistic optimization of the surface and bulk morphology of the ternary active layer suppresses the attenuation of J and FF. The smooth surface and suitable phase separation size effectively guarantee the separation, transport and extraction of the charge. Moreover, the addition of ICBA can significantly improve the hole transport capacity of the active layer, and the optimal hole mobility is 5.13 - 10"4 cm²VS. Finally, the TOSCs with 10% weight ratio of ICBA gives the optimal PCE of 9.24% and ideality factor of 2.3.
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http://dx.doi.org/10.1166/jnn.2021.19493DOI Listing
November 2021

Safety measures for COVID-19 do not compromise the outcomes of patients undergoing primary percutaneous coronary intervention: a single center retrospective study.

Sci Rep 2021 05 11;11(1):9959. Epub 2021 May 11.

Center of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, 5 Jingyuan Road, Beijing, 100043, China.

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting nearly 170 countries/regions and millions of patients worldwide. Patients with acute myocardial infarction (AMI) still need to be treated at percutaneous coronary intervention (PCI) centers with relevant safety measures. This retrospective study was conducted to assess the therapeutic outcomes of PCI performed under the safety measures and normal conditions. AMI patients undergoing PCI between January 24 to April 30, 2020 were performed under safety measures for COVID-19. Patients received pulmonary computed tomography (CT) and underwent PCI in negative pressure ICU. Cardiac catheterization laboratory (CCL) staff and physicians worked with level III personal protection. Demographic and clinical data, such as door-to-balloon (DTB) time, operation time, complications for patients in this period (COVID-19 group) and the same period in 2019 (2019 group) were retrieved and analyzed. COVID-19 and 2019 groups had 37 and 96 patients, respectively. There was no significant difference in age, gender, BMI and comorbidity between the two groups. DTB time and operation time were similar between the two groups (60.0 ± 12.39 vs 58.83 ± 12.85 min, p = 0.636; 61.46 ± 9.91 vs 62.55 ± 10.72 min, p = 0.592). Hospital stay time in COVID-19 group was significantly shorter (6.78 ± 2.14 vs 8.85 ± 2.64 days, p < 0.001). The incidences of malignant arrhythmia and Takotsubo Syndrome in COVID-19 group were higher than 2019 group significantly (16.22% vs 5.21%, p = 0.039; 10.81% vs 1.04% p = 0.008). During hospitalization and 3-month follow-up, the incidence of major adverse cardiovascular events and mortality in the two groups were statistically similar (35.13% vs 14.58%, p = 0.094; 16.22% vs 8.33%, p = 0.184). The risk of major adverse cardiac events (MACE) was associated with cardiogenic shock (OR, 11.53; 95% CI, 2.888-46.036; p = 0.001), malignant arrhythmias (OR, 7.176; 95% CI, 1.893-27.203; p = 0.004) and advanced age (≥ 75 years) (OR, 6.718; 95% CI, 1.738-25.964; p = 0.006). Cardiogenic shock (OR, 17.663; 95% CI, 5.5-56.762; p < 0.001) and malignant arrhythmias (OR, 4.659; 95% CI, 1.481-14.653; p = 0.008) were also associated with death of 3 months. Our analysis showed that safety measures undertaken in this hospital, including screening of COVID-19 infection and use of personal protection equipment for conducting PCI did not compromise the surgical outcome as compared with PCI under normal condition, although there were slight increases in incidence of malignant arrhythmia and Takotsubo Syndrome.
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http://dx.doi.org/10.1038/s41598-021-89419-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113542PMC
May 2021

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features.

Nat Commun 2021 05 11;12(1):2722. Epub 2021 May 11.

Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.
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http://dx.doi.org/10.1038/s41467-021-22890-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113327PMC
May 2021

Resolving the spatial and cellular architecture of lung adenocarcinoma by multiregion single-cell sequencing.

Cancer Discov 2021 May 10. Epub 2021 May 10.

Pulmonary Medicine, UT-MD Anderson Cancer Center.

Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from 5 early-stage LUADs and 14 multi-region normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages and inflammatory dendritic cells. We further find that the LUAD ligand-receptor interactome harbors increased expression of epithelial CD24 which mediates pro-tumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1285DOI Listing
May 2021

Anisotropic -Factor and Spin-Orbit Field in a Germanium Hut Wire Double Quantum Dot.

Nano Lett 2021 May 29;21(9):3835-3842. Epub 2021 Apr 29.

CAS Key Laboratory of Quantum Information, University of Science and Technology of China, Hefei, Anhui 230026, China.

Holes in nanowires have drawn significant attention in recent years because of the strong spin-orbit interaction, which plays an important role in constructing Majorana zero modes and manipulating spin-orbit qubits. Here, from the strongly anisotropic leakage current in the spin blockade regime for a double dot, we extract the full -tensor and find that the spin-orbit field is in plane with an azimuthal angle of 59° to the axis of the nanowire. The direction of the spin-orbit field indicates a strong spin-orbit interaction along the nanowire, which may have originated from the interface inversion asymmetry in Ge hut wires. We also demonstrate two different spin relaxation mechanisms for the holes in the Ge hut wire double dot: spin-flip co-tunneling to the leads, and spin-orbit interaction within the double dot. These results help establish feasibility of a Ge-based quantum processor.
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http://dx.doi.org/10.1021/acs.nanolett.1c00263DOI Listing
May 2021

[Kinematics analysis and scale optimization of four degree of freedom generalized spherical parallel mechanism for ankle joint rehabilitation].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Apr;38(2):286-294

School of Mechanical Engineering, Hebei University of Technology, Tianjin 300401, P.R.China.

By analyzing the physiological structure and motion characteristics of human ankle joint, a four degree of freedom generalized spherical parallel mechanism is proposed to meet the needs of ankle rehabilitation. Using the spiral theory to analyze the motion characteristics of the mechanism and based on the method of describing the position with spherical coordinates and the posture with Euler Angle, the inverse solution of the closed vector equation of mechanism position is established. The workspace of mechanism is analyzed according to the constraint conditions of inverse solution. The workspace of the moving spherical center of the mechanism is used to match the movement space of the tibiotalar joint, and the workspace of the dynamic platform is used to match the movement space of subtalar joint. Genetic algorithm is used to optimize the key scale parameters of the mechanism. The results show that the workspace of the generalized spherical parallel mechanism can satisfy the actual movement space of human ankle joint rehabilitation. The results of this paper can provide theoretical basis and experimental reference for the design of ankle joint rehabilitation robot with high matching degree.
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http://dx.doi.org/10.7507/1001-5515.202006080DOI Listing
April 2021

A polysaccharide of PFP-1 from Pleurotus geesteranus attenuates alcoholic liver diseases via Nrf2 and NF-κB signaling pathways.

Food Funct 2021 May 28;12(10):4591-4605. Epub 2021 Apr 28.

College of Life Science, Shandong Agricultural University, Taian, 271018, PR China.

A polysaccharide named PFP-1 was isolated from the Pleurotus geesteranus fruiting body, and potential investigations on ameliorating oxidative stress and liver injury against alcoholic liver disease (ALD) were performed in mice. The animal studies demonstrated that PFP-1 had hepatoprotective effects by improving hepatocellular histopathology, modulating alcohol metabolisms and restoring the serum lipid levels. Besides, PFP-1 could attenuate oxidative stress and inflammatory responses by activating the Nrf2-mediated signal pathways and regulating the TLR4-mediated NF-κB signal pathways. The characterization indicated that PFP-1 was a typical pyranose-polysaccharide in a triple-helical conformation, which was linked by t-β-Glcp, 1,6-α-Glcp and 1,2,6-α-Galp. And the characteristic properties of higher water solubility and appropriate molecular weights contributed to the superior bioactivities. The results demonstrated that PFP-1 could be used as a supplement for alleviating alcohol-induced liver damage.
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http://dx.doi.org/10.1039/d1fo00310kDOI Listing
May 2021

Research progress on hepatic machine perfusion.

Int J Med Sci 2021 3;18(9):1953-1959. Epub 2021 Mar 3.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.
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http://dx.doi.org/10.7150/ijms.56139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040389PMC
March 2021

Structural characterization and amelioration of sulfated polysaccharides from Ganoderma applanatum residue against CCl-induced hepatotoxicity.

Int Immunopharmacol 2021 Jul 31;96:107554. Epub 2021 Mar 31.

College of Life Science, Shandong Agricultural University, Taian 271018, PR China. Electronic address:

Natural polysaccharides and their derivatives have attracted academic attention due to their extensive physiological activities. However, the hepatoprotective effects against carbon tetrachloride (CCl) toxicity have not been well elucidated. The objectives of this study were to characterize the structural properties of sulfated Ganoderma applanatum residue polysaccharides (SGRP) and to evaluate their inhibitory effects on liver fibrosis caused by oxidative stress and inflammation. Our in vivo study showed that SGRP was hepatoprotective in CCl-induced chronic liver injury mice. It reduced the histopathological damages, down-regulated CYP2E1 (cytochrome P450 2E1) expression, reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, improved the anti-oxidative and anti-inflammatory properties, inhibited TLR4/NF-κB signaling pathway, and reduced the release of inflammatory cytokines. The structural studies indicated that SGRP is a heteropolysaccharide with 7.8% sulfur content and α-linked residue. Our study projects SGRP as a potential candidate in anti-fibrosis treatment by using it as a food supplement or in medicines produced by pharmaceutical industries.
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http://dx.doi.org/10.1016/j.intimp.2021.107554DOI Listing
July 2021

Single-Cell Expression Landscape of SARS-CoV-2 Receptor and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Severely symptomatic COVID-19 is associated with lung inflammation, pneumonia, and respiratory failure, thereby raising concerns of elevated risk of COVID-19-associated mortality among lung cancer patients. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 entry into lung cells. The single-cell expression landscape of and other SARS-CoV-2-related genes in pulmonary tissues of lung cancer patients remains unknown. We sought to delineate single-cell expression profiles of and other SARS-CoV-2-related genes in pulmonary tissues of lung adenocarcinoma (LUAD) patients. We examined the expression levels and cellular distribution of and SARS-CoV-2-priming proteases and in 5 LUADs and 14 matched normal tissues by single-cell RNA-sequencing (scRNA-seq) analysis. scRNA-seq of 186,916 cells revealed epithelial-specific expression of , , and . Analysis of 70,030 LUAD- and normal-derived epithelial cells showed that levels were highest in normal alveolar type 2 (AT2) cells and that was expressed in 65% of normal AT2 cells. Conversely, the expression of was highest and most frequently detected (75%) in lung cells with malignant features. -positive cells co-expressed genes implicated in lung pathobiology, including COPD-associated , and the scavengers and . Notably, the viral scavenger was significantly positively correlated with expression in AT2 cells. We describe normal and tumor lung epithelial populations that express SARS-CoV-2 receptor and proteases, as well as major host defense genes, thus comprising potential treatment targets for COVID-19 particularly among lung cancer patients.
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http://dx.doi.org/10.3390/cancers13061250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998226PMC
March 2021

Genome-Scale Analysis Identified NID2, SPARC, and MFAP2 as Prognosis Markers of Overall Survival in Gastric Cancer.

Med Sci Monit 2021 Mar 24;27:e929558. Epub 2021 Mar 24.

Department of Gastric Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China (mainland).

BACKGROUND Gastric cancer is the most common gastrointestinal tumor, and the rates of recurrence and metastasis are high. Research results on molecular biomarkers used for prognosis of gastric cancer remain inconclusive. This study aimed to explore the gene expression module of gastric cancer and to determine potential prognostic biomarkers. MATERIAL AND METHODS Three microarray datasets (GSE13911, GSE79973, and GSE29272) from Gene Expression Omnibus (GEO), including 206 pairs of gastric tumors and adjacent normal samples, were used for analysis of differentially expressed genes (DEGs). The 3 microarray datasets yielded 144 genes associated with the progression and prognosis of gastric cancer. After this, a risk score model was developed for result validation using an independent dataset from The Cancer Genome Atlas. RESULTS The validation of the independent dataset showed significantly increased NID2, SPARC, and MFAP2 expression in gastric tumor tissues, which were associated with poor outcomes in gastric cancer patients. Moreover, the high risk score obtained was associated with poor overall survival (HR: 1.787; 1.069-2.986; P=0.027). Subgroup analyses revealed that these significant prognostic values were detected in patients aged <65.0 years, tumors in the antrum/distal colon, grade 3 tumors, or TNM-M0 stages of cancer. CONCLUSIONS The findings of this study show that NID2, SPARC, and MFAP2 are upregulated in gastric tumor tissues and are significantly associated with poor overall survival. Therefore, the predictive values of the risk score model employed for the prognosis of gastric cancer could be improved by using these 3 upregulated DEGs.
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http://dx.doi.org/10.12659/MSM.929558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006563PMC
March 2021

Competitive cocrystallization and its application in the separation of flavonoids.

IUCrJ 2021 Mar 21;8(Pt 2):195-207. Epub 2021 Jan 21.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Recently, cocrystallization has been widely employed to tailor physicochemical properties of drugs in the pharmaceutical field. In this study, cocrystallization was applied to separate natural compounds with similar structures. Three flavonoids [baicalein (BAI), quercetin (QUE) and myricetin (MYR)] were used as model compounds. The coformer caffeine (CAF) could form cocrystals with all three flavonoids, namely BAI-CAF (cocrystal 1), QUE-CAF (cocrystal 2) and MYR-CAF (cocrystal 3). After adding CAF to methanol solution containing MYR and QUE (or QUE and BAI), cocrystal 3 (or cocrystal 2) preferentially formed rather than cocrystal 2 (or cocrystal 1), indicating that flavonoid separation could be achieved by competitive cocrystallization. After co-mixing the slurry of two flavonoids with CAF followed by centrifugation, the resolution ratio that could be achieved was 70-80% with purity >90%. Among the three cocrystals, cocrystal 3 showed the lowest formation constant with a negative Gibbs free energy of nucleation and the highest energy gap. Hirshfeld surface analysis and density of states analysis found that cocrystal 3 had the highest strong interaction contribution and the closest electronic density, respectively, followed by cocrystal 2 and cocrystal 1, suggesting CAF could competitively form a cocrystal with MYR much more easily than QUE and BAI. Cocrystallization is a promising approach for green and effective separation of natural products with similar chemical structures.
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http://dx.doi.org/10.1107/S2052252520015997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924225PMC
March 2021

Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery.

Immunity 2021 Mar;54(3):586-602.e8

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.

To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRβ chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A02:01 display library. These included a peptide from the epithelial protein TMEM161A, which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virus and E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specific T cells in tumor infiltrates and that pathogen cross-reactivity may be a feature of multiple cancers. The approach and analytical pipelines generated in this work, as well as the specificity groups defined here, present a resource for understanding the T cell response in cancer.
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http://dx.doi.org/10.1016/j.immuni.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960510PMC
March 2021

Zinc Finger Protein CTCF Regulates Extracellular Matrix (ECM)-Related Gene Expression Associated With the Wnt Signaling Pathway in Gastric Cancer.

Front Oncol 2020 16;10:625633. Epub 2021 Feb 16.

Faculty of Medical Laboratory Science, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients. Interestingly, putative CCCTC-binding factor (CTCF) regulatory elements were identified within the promoters of these ECM-related genes and were confirmed by chromatin immunoprecipitation sequencing (ChIP-Seq). CTCF binding sites also overlapped with histone activation markers, indicating direct regulation. In addition, CTCF was also correlated with the Wnt signaling pathway. A comparison of human GC cell lines with high or low expression of ECM-related genes revealed different levels of tumor aggressiveness, suggesting the cancer development-promoting functions of ECM-related genes. Furthermore, CTCF regulated COL1A1 and COLA31 expression . Silencing CTCF or COL1A1/COL1A3 markedly inhibited cell growth and migration in the metastatic GC cell line BGC823. Collectively, this ECM-related 7-gene signature provides a novel insight for survival prediction among GC patients. The zinc finger protein CTCF regulates ECM-related genes, thereby promoting GC cell growth and migration.
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http://dx.doi.org/10.3389/fonc.2020.625633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921701PMC
February 2021
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