Publications by authors named "Peng He"

418 Publications

Many Birds, One Stone: A Smart Nanodevice for Ratiometric Dual-Spectrum Assay of Intracellular MicroRNA and Multimodal Synergetic Cancer Therapy.

ACS Nano 2021 Apr 5. Epub 2021 Apr 5.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, Ministry of Education, Shandong Key Laboratory of Biochemical Analysis, and College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P.R. China.

The development of a theragnostic platform integrating precise diagnosis and effective treatment is significant but still extremely challenging. Herein, an integrated smart nanodevice composed of Au@CuS@polydopamine nanoparticles (ACSPs) and fuel DNA-conjugated tetrahedral DNA nanostructures (fTDNs) was constructed, in which the ACSP nanoprobe played multiple key roles in antitumor therapy as well as monitoring of microRNAs (miRNAs) in cancer cells. Regarding the analysis, the ACSP probe contained two optical properties: excellent surface-enhanced Raman scattering (SERS) enhancement and high fluorescence (FL) quenching performance. Employing the ACSPs as the high-efficiency detection substrate combined with the fTDN-assisted DNA walking nanomachines as the superior amplification strategy, a SERS-FL dual-spectrum biosensor was constructed, which achieved an ultralow background signal and excellent sensitivity with detection limits of 0.11 pM and 4.95 aM by FL and SERS, respectively. Moreover, the rapid FL imaging and precise SERS quantitative detection for miRNA in cancer cells were also achieved by dual-signal ratio strategy, improving the accuracy of diagnosis. Regarding the therapeutic application, due to the high reactive oxygen species generation ability and excellent photothermal conversion efficiency, the ACSPs can also act as an all-in-one nanoagent for multimodal collaborative tumor therapy. Significantly, both and experiments confirmed its high biological safety and strong anticancer effect, indicating its promising theragnostic applications.
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http://dx.doi.org/10.1021/acsnano.0c10844DOI Listing
April 2021

Phase I trial of MEDI3726, a prostate-specific membrane antigen-targeted antibody-drug conjugate, in patients with mCRPC after failure of abiraterone or enzalutamide.

Clin Cancer Res 2021 Apr 1. Epub 2021 Apr 1.

Prostate and Urologic Cancers Program, Yale Cancer Center.

Purpose: MEDI3726 is an antibody-drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This Phase 1 study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.

Experimental Design: MEDI3726 was administered at 0.015-0.3 mg/kg IV Q3W until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD)/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of {greater than or equal to}50% after {greater than or equal to}12 weeks, and/or decrease from {greater than or equal to}5 to <5 circulating tumor cells/7.5 mL blood.

Results: Between 1 February 2017 and 13 November 2019, 33 patients received MEDI3726. By the data cutoff (17 January 2020), treatment-related AEs (TRAEs) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued due to TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3-1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%) and the incidence was 13/32 (40.6%).

Conclusions: Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4528DOI Listing
April 2021

Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

Lancet Infect Dis 2021 Mar 24. Epub 2021 Mar 24.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. Electronic address:

Background: Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study.

Methods: We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing.

Findings: Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90%] of 20 in the 50 μg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 μg group, 50 [33%] of 150 in the two-dose 50 μg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 μg group, and 65 [43%] of 150 in the three-dose 50 μg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 μg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 μg vaccine group, two [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 μg vaccine group, and six [4%] in the three-dose 50 μg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 μg vaccine group, and five [3%] in the three-dose 50 μg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 μg vaccine group, and two [1%] in the three-dose 50 μg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 μg group and 72% (108 of 150) in the 50 μg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6-23·1) in the 25 μg group and 14·1 (10·8-18·3) in the 50 μg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8-128·5) in the 25 μg group and 69·1 (53·0-90·0) in the 50 μg group.

Interpretation: The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy.

Funding: National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00127-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990482PMC
March 2021

Social network architecture and the tempo of cumulative cultural evolution.

Proc Biol Sci 2021 Mar 10;288(1946):20203107. Epub 2021 Mar 10.

Department of Biology, University of Konstanz, Konstanz, Germany.

The ability to build upon previous knowledge-cumulative cultural evolution-is a hallmark of human societies. While cumulative cultural evolution depends on the interaction between social systems, cognition and the environment, there is increasing evidence that cumulative cultural evolution is facilitated by larger and more structured societies. However, such effects may be interlinked with patterns of social wiring, thus the relative importance of social network architecture as an additional factor shaping cumulative cultural evolution remains unclear. By simulating innovation and diffusion of cultural traits in populations with stereotyped social structures, we disentangle the relative contributions of network architecture from those of population size and connectivity. We demonstrate that while more structured networks, such as those found in multilevel societies, can promote the recombination of cultural traits into high-value products, they also hinder spread and make products more likely to go extinct. We find that transmission mechanisms are therefore critical in determining the outcomes of cumulative cultural evolution. Our results highlight the complex interaction between population size, structure and transmission mechanisms, with important implications for future research.
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http://dx.doi.org/10.1098/rspb.2020.3107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944107PMC
March 2021

Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus.

Carbohydr Polym 2021 May 14;260:117797. Epub 2021 Feb 14.

Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, United States; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, United States. Electronic address:

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.
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http://dx.doi.org/10.1016/j.carbpol.2021.117797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882221PMC
May 2021

Hematuria was a high risk for renal progression and ESRD in immunoglobulin a nephropathy: a systematic review and meta-analysis.

Ren Fail 2021 Dec;43(1):488-499

Department of Nephrology, State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.

The relationship between hematuria, a typical presentation of immunoglobulin A nephropathy (IgAN), and long-term adverse prognosis of these patients is still controversial. This meta-analysis aims to clarify the effect of hematuria on renal outcomes in IgAN. Observational cohort studies reporting associations between various forms of hematuria and renal outcomes among IgAN patients were identified from the PubMed and Embase databases. The pooled adjusted risk ratios (RRs) were computed with random effects models. Thirteen studies encompassing 5660 patients with IgAN were included. Patients with initial hematuria did not have a significantly increased risk of developing end-stage renal disease (ESRD) compared with those without hematuria (RR, 1.32; 95% CI, 0.87-2.00;  = .19). However, initial microscopic hematuria was associated with an 87% increase in the risk of ESRD (RR, 1.87; 95% CI, 1.40-2.50;  < .001), while macroscopic hematuria was associated with a 32% decrease in the risk of ESRD (RR, 0.68; 95% CI, 0.58-0.79;  < .001). Additionally, persistent hematuria might be an independent risk factor for ESRD or a 50% decline in eGFR. Among IgAN patients, hematuria, including initial microscopic hematuria and even persistent hematuria, was possibly associated with renal progression and ESRD. However, independent of other classical predictors, initial macroscopic hematuria might be a protective factor for IgAN.
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http://dx.doi.org/10.1080/0886022X.2021.1879852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946061PMC
December 2021

Prevalence and risk factors of relapse in patients with ANCA-associated vasculitis receiving cyclophosphamide induction: a systematic review and meta-analysis of large observational studies.

Rheumatology (Oxford) 2021 Mar;60(3):1067-1079

Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Background: Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse.

Methods: We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed.

Results: Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10-0.14), 0.33 (0.29-0.38), and 0.47 (0.42-0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine).

Conclusions: Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.
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http://dx.doi.org/10.1093/rheumatology/keaa667DOI Listing
March 2021

Ascorbic acid analogue 6-Deoxy-6-[F] fluoro-L-ascorbic acid as a tracer for identifying human colorectal cancer with SVCT2 overexpression.

Transl Oncol 2021 May 4;14(5):101055. Epub 2021 Mar 4.

Department of Nuclear Medicine & Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

L-ascorbic acid (AA) was reported to have an anti-cancer effect over 40 years. In recent years, several ongoing clinical trials are exploring the safety and efficacy of intravenous high-dose AA for cancer treatment. The lack of appropriate imaging modality limits the identification of potentially suitable patients for AA treatment. This study focuses on identifying AA-sensitive tumor cells using molecular imaging. 6-Deoxy-6-[F] fluoro-L-ascorbic Acid (F-DFA), a structural analog of AA, was synthesized and labeled to visualize the metabolism of AA in vivo. Colorectal cancer (CRC) cell lines with high and low expression of sodium-dependent vitamin C transporters 2 (SVCT2) were used for a series of cellular uptake tests. PET imaging was performed on xenograft tumor-bearing mice. More AA uptake was observed in CRC cells with high SVCT2 expression than in cells with low SVCT2 expression. The substrate (unlabeled AA) can competitively inhibit the F-DFA tracer uptake by CRC cells. The biodistribution of F-DFA in mice showed high radioactivity was seen in organs such as adrenal glands, kidneys, and liver that were known to have high concentrations of AA. Both PET imaging and tissue distribution showed that cancer cells with high SVCT2 expression enhanced the accumulation of F-DFA in mice after tumor formation. Immunohistochemistry was used to verify the corresponding results. As a radiotracer, F-DFA can provide powerful imaging information to identify tumor with high affinity of AA, and SVCT2 can be a potential biomarker in this process.
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http://dx.doi.org/10.1016/j.tranon.2021.101055DOI Listing
May 2021

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Authors:
Christoph Muus Malte D Luecken Gökcen Eraslan Lisa Sikkema Avinash Waghray Graham Heimberg Yoshihiko Kobayashi Eeshit Dhaval Vaishnav Ayshwarya Subramanian Christopher Smillie Karthik A Jagadeesh Elizabeth Thu Duong Evgenij Fiskin Elena Torlai Triglia Meshal Ansari Peiwen Cai Brian Lin Justin Buchanan Sijia Chen Jian Shu Adam L Haber Hattie Chung Daniel T Montoro Taylor Adams Hananeh Aliee Samuel J Allon Zaneta Andrusivova Ilias Angelidis Orr Ashenberg Kevin Bassler Christophe Bécavin Inbal Benhar Joseph Bergenstråhle Ludvig Bergenstråhle Liam Bolt Emelie Braun Linh T Bui Steven Callori Mark Chaffin Evgeny Chichelnitskiy Joshua Chiou Thomas M Conlon Michael S Cuoco Anna S E Cuomo Marie Deprez Grant Duclos Denise Fine David S Fischer Shila Ghazanfar Astrid Gillich Bruno Giotti Joshua Gould Minzhe Guo Austin J Gutierrez Arun C Habermann Tyler Harvey Peng He Xiaomeng Hou Lijuan Hu Yan Hu Alok Jaiswal Lu Ji Peiyong Jiang Theodoros S Kapellos Christin S Kuo Ludvig Larsson Michael A Leney-Greene Kyungtae Lim Monika Litviňuková Leif S Ludwig Soeren Lukassen Wendy Luo Henrike Maatz Elo Madissoon Lira Mamanova Kasidet Manakongtreecheep Sylvie Leroy Christoph H Mayr Ian M Mbano Alexi M McAdams Ahmad N Nabhan Sarah K Nyquist Lolita Penland Olivier B Poirion Sergio Poli CanCan Qi Rachel Queen Daniel Reichart Ivan Rosas Jonas C Schupp Conor V Shea Xingyi Shi Rahul Sinha Rene V Sit Kamil Slowikowski Michal Slyper Neal P Smith Alex Sountoulidis Maximilian Strunz Travis B Sullivan Dawei Sun Carlos Talavera-López Peng Tan Jessica Tantivit Kyle J Travaglini Nathan R Tucker Katherine A Vernon Marc H Wadsworth Julia Waldman Xiuting Wang Ke Xu Wenjun Yan William Zhao Carly G K Ziegler

Nat Med 2021 03 2;27(3):546-559. Epub 2021 Mar 2.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2TMPRSS2 cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.
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http://dx.doi.org/10.1038/s41591-020-01227-zDOI Listing
March 2021

Reversal of Multidrug Resistance by Apolipoprotein A1-Modified Doxorubicin Liposome for Breast Cancer Treatment.

Molecules 2021 Feb 26;26(5). Epub 2021 Feb 26.

Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai 201203, China.

Multidrug resistance (MDR) remains a major problem in cancer therapy and is characterized by the overexpression of p-glycoprotein (P-gp) efflux pump, upregulation of anti-apoptotic proteins or downregulation of pro-apoptotic proteins. In this study, an Apolipoprotein A1 (ApoA1)-modified cationic liposome containing a synthetic cationic lipid and cholesterol was developed for the delivery of a small-molecule chemotherapeutic drug, doxorubicin (Dox) to treat MDR tumor. The liposome-modified by ApoA1 was found to promote drug uptake and elicit better therapeutic effects than free Dox and liposome in MCF-7/ADR cells. Further, loading Dox into the present ApoA1-liposome systems enabled a burst release at the tumor location, resulting in enhanced anti-tumor effects and reduced off-target effects. More importantly, ApoA1-lip/Dox caused fewer adverse effects on cardiac function and other organs in 4T1 subcutaneous xenograft models. These features indicate that the designed liposomes represent a promising strategy for the reversal of MDR in cancer treatment.
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http://dx.doi.org/10.3390/molecules26051280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956628PMC
February 2021

Generated SecPen_NY-ESO-1_ubiquitin-pulsed dendritic cell cancer vaccine elicits stronger and specific T cell immune responses.

Acta Pharm Sin B 2021 Feb 25;11(2):476-487. Epub 2020 Aug 25.

Shanghai Engineering Research Center of ImmunoTherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, China.

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38 tumor cells or DC vaccines. The results show that SNU was successfully expressed. This strategy made NY-ESO-1 entering cytoplasm of BMDCs more efficiently and degraded mainly by proteasome. As we expected, mature BMDCs expressed higher CD40, CD80 and CD86 than immature BMDCs. Thus, the PBMCs released more IFN- and TNF- when stimulated with DC-SNU again. What's more, the PBMCs induced stronger and specific cytotoxicity towards MC38 tumor cells. Given the above, it demonstrated that DC-SNU loaded with SecPen and ubiquitin-fused NY-ESO-1 could elicit stronger and specific T cell immune responses. This strategy can be used as a platform for DC vaccine preparation and applied to various cancers treatment.
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http://dx.doi.org/10.1016/j.apsb.2020.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893120PMC
February 2021

Preparation of Low Molecular Weight Heparin from a Remodeled Bovine Intestinal Heparin.

J Med Chem 2021 Feb 15;64(4):2242-2253. Epub 2021 Feb 15.

Department of Chemistry & Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York 12180, United States.

Bovine intestinal heparins are structurally distinct from porcine intestinal heparins and exhibit lower specific anticoagulant activity (units/mg). The reduced content of -sulfo, 3--sulfo glucosamine, the central and critical residue in heparin's antithrombin III binding site, is responsible for bovine intestinal heparin's reduced activity. Previous studies demonstrate that treatment of bovine intestinal heparin with 3--sulfotransferase in the presence of 3'-phosphoadenosine-5'-phosphosulfate afforded remodeled bovine heparin with an enhanced activity reaching the United States Pharmacopeia's requirements. Starting from this remodeled bovine intestinal heparin, we report the preparation of a bovine intestinal low molecular weight heparin having the same structural properties and anti-factor IIa and anti-factor Xa activities of Enoxaparin. Moreover, this bovine intestinal heparin-derived "Enoxaparin" showed comparable platelet factor-4 binding affinity, suggesting that it should exhibit similarly low levels of heparin induced thrombocytopeneia, HIT.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02019DOI Listing
February 2021

Estimation of Winter Wheat Yield in Arid and Semiarid Regions Based on Assimilated Multi-Source Sentinel Data and the CERES-Wheat Model.

Sensors (Basel) 2021 Feb 10;21(4). Epub 2021 Feb 10.

College of Agriculture, Shanxi Agricultural University, Taigu 030801, China.

The farmland area in arid and semiarid regions accounts for about 40% of the total area of farmland in the world, and it continues to increase. It is critical for global food security to predict the crop yield in arid and semiarid regions. To improve the prediction of crop yields in arid and semiarid regions, we explored data assimilation-crop modeling strategies for estimating the yield of winter wheat under different water stress conditions across different growing areas. We incorporated leaf area index (LAI) and soil moisture derived from multi-source Sentinel data with the CERES-Wheat model using ensemble Kalman filter data assimilation. According to different water stress conditions, different data assimilation strategies were applied to estimate winter wheat yields in arid and semiarid areas. Sentinel data provided LAI and soil moisture data with higher frequency (<14 d) and higher precision, with root mean square errors (RMSE) of 0.9955 m m and 0.0305 cm cm, respectively, for data assimilation-crop modeling. The temporal continuity of the CERES-Wheat model and the spatial continuity of the remote sensing images obtained from the Sentinel data were integrated using the assimilation method. The RMSE of LAI and soil water obtained by the assimilation method were lower than those simulated by the CERES-Wheat model, which were reduced by 0.4458 m m and 0.0244 cm cm, respectively. Assimilation of LAI independently estimated yield with high precision and efficiency in irrigated areas for winter wheat, with RMSE and absolute relative error (ARE) of 427.57 kg ha and 6.07%, respectively. However, in rain-fed areas of winter wheat under water stress, assimilating both LAI and soil moisture achieved the highest accuracy in estimating yield (RMSE = 424.75 kg ha, ARE = 9.55%) by modifying the growth and development of the canopy simultaneously and by promoting soil water balance. Sentinel data can provide high temporal and spatial resolution data for deriving LAI and soil moisture in the study area, thereby improving the estimation accuracy of the assimilation model at a regional scale. In the arid and semiarid region of the southeastern Loess Plateau, assimilation of LAI independently can obtain high-precision yield estimation of winter wheat in irrigated area, while it requires assimilating both LAI and soil moisture to achieve high-precision yield estimation in the rain-fed area.
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http://dx.doi.org/10.3390/s21041247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916384PMC
February 2021

Two carboxylesterase genes in Plutella xylostella associated with sex pheromones and plant volatiles degradation.

Pest Manag Sci 2021 Feb 1. Epub 2021 Feb 1.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, P. R. China.

Background: Carboxyl/cholinesterases (CCEs) are thought to play a pivotal role in the degradation of sex pheromones and plant-derived odorants in insects, but their exact biochemistry and physiological functions remain unclear.

Results: In this study, two paralogous antennae-enriched CCEs from Plutella xylostella (PxylCCE16a and 16c) were identified and functionally characterized. High-purity protein preparations of active recombinant PxylCCE16a and 16c have been obtained from Sf9 insect cells by Ni affinity purification. Our results revealed that the purified recombinant PxylCCE016c is able to degrade two sex pheromone components Z9-14:Ac and Z11-16:Ac at 27.64 ± 0.79% and 24.40 ± 3.07%, respectively, while PxylCCE016a presented relatively lower activity. Additionally, a similar difference in activity was measured in plant-derived odorants. Furthermore, both CCEs displayed obvious preferences for the two sex pheromone components, especially on Z11-16:Ac (K values are in the range 7.82-45.06 μmol L ) which much lower than plant odorants (K values are in the range 1290-4030 μmol L ). Furthermore, the activity of the two newly identified CCEs is pH-dependent. The activity at pH 6.5 is obviously higher than that at pH 5.0. Interestingly, only PxylCCE016c can be inhibited by a common esterase inhibitor triphenyl phosphate (TPP) with LC of 1570 ± 520 μmol L .

Conclusion: PxylCCE16c plays a more essential role in odorant degradation than PxylCCE16a. Moreover, the current study provides novel potential pesticide targets for the notorious moth Plutella xylostella.
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http://dx.doi.org/10.1002/ps.6302DOI Listing
February 2021

Graphene Quantum Dots with Pyrrole N and Pyridine N: Superior Reactive Oxygen Species Generation Efficiency for Metal-Free Sonodynamic Tumor Therapy.

Small 2021 Mar 28;17(10):e2004867. Epub 2021 Jan 28.

Joint Laboratory of Graphene Materials and Applications, State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

Those responsible for the development of sonosensitizers are faced with a dilemma between high sonosensitization efficacy and good biosecurity that limited the development of sonodynamic therapy (SDT). Herein, inspired by the intriguing therapeutic features of SDT and the potential catalytic activity of graphene quantum dots, the potential of N-doped graphene quantum dots (N-GQDs) to act as a sonosensitizer is demonstrated. The superior sonosensitization effect of N-GQDs is believed to be three to five times higher than that of traditional sonosensitizers (such as porphyrin, porphyrin Mn, porphyrin Zn, TiO , etc.). More importantly, the sonochemical mechanism of N-GQDs is revealed. Pyrrole N and pyridine N are believed to form catalytic centers in sonochemical processing of N-GQDs. This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of carbon nanostructure. Moreover, N-GQDs modified by folic acid (FA-N-GQDs) show a high marker rate for tumor cells (greater than 96%). Both in vitro and in vivo therapeutic results have exhibited high tumor inhibition efficiency (greater than 90%) of FA-N-GQDs as sonosensitizers while the oxidative stress response of tumor cells is activated through the PEX pathway and induced apoptosis via the p53 pathway.
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http://dx.doi.org/10.1002/smll.202004867DOI Listing
March 2021

Detection of necroptosis by phospho-MLKL immunohistochemical labeling.

STAR Protoc 2021 Mar 30;2(1):100251. Epub 2020 Dec 30.

State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital of Xiamen University, Cancer Research Center of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.

TNF-induced necroptosis is involved in many physiological and pathological processes. Phospho-MLKL is a hallmark of necroptosis. Cecum is a sensitive organ with extensive necroptosis responses to TNF . Here, taking advantage of commercially available mouse TNF and easily accessible reagents and materials, we systematically provide a detailed and highly versatile protocol of detecting necroptosis signaling in mouse cecum by immunohistochemical labeling, which can also be used in other tissues or antibodies in immunohistochemical staining. For complete details on the use and execution of this protocol, please refer to Yang et al. (2020) and Chen et al. (2015).
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http://dx.doi.org/10.1016/j.xpro.2020.100251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797912PMC
March 2021

RNAi-mediated knockdown of PFK1 decreases the invasive capability and metastasis of nasopharyngeal carcinoma cell line, CNE-2.

Cell Cycle 2021 Jan 6;20(2):154-165. Epub 2021 Jan 6.

Department of Otolaryngology Head and Neck Surgery, The 5th Affiliated Hospital of Sun Yat-sen University , Zhuhai, China.

Nasopharyngeal carcinoma (NPC) is the most prevailing malignancy of the head and neck with unique geographic distribution. Southern China has one of the highest incidence rates of NPC in the world. Although radiotherapy and chemotherapy are the most important treatment modalities for NPC, recurrence, and metastasis severely interfere with the survival quality of patients. It is much-needed to find an effective method of NPC treatment with a good prognosis such as gene therapy. PFK1, a key regulatory enzyme of glycolysis, is frequently shown to be amplified and overexpressed in a variety of human cancers. However, the function of PFK1 and molecular mechanism in NPC is elusive. Here, we knockdown PFK1 expression by utilizing DNA vector-based RNA Interference. Western blotting and real-time PCR show that the expression of PFK1 is efficiently down-regulated in both protein and mRNA levels by stable transfection with PFK1 siRNA expression vector. In addition, stable knockdown of PFK1 expression inhibits cell growth, induces apoptosis, decreases the invasive capability and metastasis in the CNE2 human NPC cell line. This present study finds the importance of PFK1 which can be worked as a novel target in NPC treatment and holds great potential to be extended to other malignant cancers.
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http://dx.doi.org/10.1080/15384101.2020.1866279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889105PMC
January 2021

Study on detoxification and removal mechanisms of hexavalent chromium by microorganisms.

Ecotoxicol Environ Saf 2021 Jan 7;208:111699. Epub 2020 Dec 7.

Department of Geosciences, Idaho State University, Pocatello, ID 83209, USA.

Extensive industrial activities have led to an increase of the content of chromium in the environment, which causes serious pollution to the surrounding water, soil and atmosphere. The enrichment of chromium in the environment through the food chain ultimately affects human health. Therefore, the remediation of chromium pollution is crucial to development of human society. A lot of scholars have paid attention to bioremediation technology owing to its environmentally friendly and low-cost. Previous reviews mostly involved pure culture of microorganisms and rarely discussed the optimization of bioreduction conditions. To make up for these shortcomings, we not only introduced in detail the conditions that affect microbial reduction but also innovatively introduced consortium which may be the cornerstone for future treatment of complex field environments. The aim of this study is to summary chromium toxicity, factors affecting microbial remediation, and methods for enhancing bioremediation. However, the actual application of bioremediation technology is still facing a major challenge. This study also put forward the current research problems and proposed future research directions, providing theoretical guidance and scientific basis for the application of bioremediation technology.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111699DOI Listing
January 2021

A candidate aldehyde oxidase in the antennae of the diamondback moth, Plutella xylostella (L.), is potentially involved in the degradation of pheromones, plant-derived volatiles and the detoxification of xenobiotics.

Pestic Biochem Physiol 2021 Jan 24;171:104726. Epub 2020 Oct 24.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, PR China. Electronic address:

Insect antennae play a fundamental role in perceiving and recognizing a broad spectrum of conventional semiochemicals and host plant-derived odors. As such, genes that are tightly associated with the antennae are thought to have olfactory-related roles related to signal transduction mechanisms. Several mechanisms suggest that enzymatic inactivation could contribute to the signal termination process, such as odorant-degrading enzymes (ODEs). To date, a few ODEs have been identified and characterized in detail in insect herbivores, but little is known about aldehyde oxidases (AOXs); moreover, direct in vivo experimental evidence is needed. AOXs are a major family of metabolic enzymes that oxidize a variety of aromatic aldehydes, and they may also play a significant role in detoxification and degradation of environmental chemical cues. Here, we report on the identification and characterization of a novel cDNA encoding the putative odorant-degrading enzyme, PxylAOX3, from the antennae of the diamondback moth, (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae). The purified recombinant protein showed a wide-range of substrate zymography oxidizing both sex pheromone compounds as well as plant-derived aldehydes with distinct activities. Our data suggest PxylAOX3 might be involved in the degradation of many structurally diverse aldehyde odorants. Furthermore, PxylAOX3 could participate in olfactory neuron protection by inactivation of redundant odorants and xenobiotic detoxification, making it a potential target for pesticide development as well.
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http://dx.doi.org/10.1016/j.pestbp.2020.104726DOI Listing
January 2021

Functional Disparity of Three Pheromone-Binding Proteins to Different Sex Pheromone Components in (Drury).

J Agric Food Chem 2021 Jan 27;69(1):55-66. Epub 2020 Dec 27.

Anhui Provincial Key Laboratory of Microbial Control, Engineering Research Center of Fungal Biotechnology, Ministry of Education School of Forestry & Landscape Architecture, Anhui Agricultural University, Hefei 230036, China.

(Drury) is a destructive invasive pest species in China that uses type II sex pheromone components. To date, however, the binding mechanisms of its sex pheromone components to their respective pheromone-binding proteins (HcunPBPs 1/2/3) have not been explored. In the current study, all three were expressed in the antennae of both sexes. The prokaryotic expression and ligand binding assays were employed to study the binding of the moth's four sex pheromone components, including two aldehydes and two epoxides, and 24 plant volatiles to the HcunPBPs. Our results showed that the abilities of these HcunPBPs to bind to the aldehydes were significantly different from binding to the epoxides. These three HcunPBPs also selectively bind to some of the plant volatiles tested. Our molecular docking results indicated that some crucial hydrophobic residues might play a role in the binding of HcunPBPs to their sex pheromone components. Three HcunPBPs have different selectivities for pheromone components with both major and minor structural differences. Our study provides a fundamental insight into the olfactory mechanism of moths at the molecular level, especially for moth species that use various type II pheromone components.
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http://dx.doi.org/10.1021/acs.jafc.0c04476DOI Listing
January 2021

Investigation of Dendrimer Transfer Behaviors at the Micro-Water/1,2-Dichloroethane Interface Facilitated by Dibenzo-18-Crown-6.

Anal Chem 2021 01 24;93(3):1515-1522. Epub 2020 Dec 24.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Trans-interfacial behaviors of multiple ionic species at the interface between two immiscible electrolyte solutions (ITIES) are of importance to biomembrane mimicking, chemical and biosensing, and interfacial molecular catalysis. Utilizing host-guest interaction to facilitate ion transfer is an effective and commonly used method to decrease the Gibbs energy of transfer of a target molecule. Herein, we investigated a facilitated ion transfer (FIT) process of poly(amidoamine)dendrimer (PAMAM, G0-G2) by dibenzo-18-crown-6 (DB18C6) at the microinterfaces between water and 1,2-dichloroethane (μ-W/DCE). Because of the host-guest interaction between a dendrimer and a ligand, negative shifts of the transfer potentials were observed using cyclic voltammetry or Osteryoung square wave voltammetry. From the FIT behavior of the dendrimer, we revealed that each DB18C6 could selectively coordinate with one amino group. We first evaluated the protonated status of the intermediate state (1:2) exactly under the conditions the dendrimer (G1) transfers across the interface using the electrochemical mass spectrometry (EC-MS)-hyphenated technique, which is much smaller than the protonated status in the water phase (1:8 to 14). Using the same methodology, we also studied the facilitated transfer behaviors of G0 and G2. Based on these results, we put forward the mechanism of the FIT process, which might involve a deprotonating process at the interface for higher-generation dendrimers.
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http://dx.doi.org/10.1021/acs.analchem.0c03815DOI Listing
January 2021

Joining of Hypereutectic Al-50Si Alloys Using Lead-Free Brazing Filler Glass in Air.

Materials (Basel) 2020 Dec 11;13(24). Epub 2020 Dec 11.

School of Materials Science and Engineering, Henan Polytechnic University, Jiaozuo 454003, China.

Hypereutectic Al-Si alloys are attractive materials in the fields of electronic packaging and aerospace. A BiO-ZnO-BO system lead-free brazing filler glass was employed to braze hypereutectic Al-50Si alloys in air. The hypereutectic Al-50Si alloys were pre-oxidized and the low-temperature glass powder was flake-shaped in the brazing process. The effects of brazing temperature and time on joints microstructure evolution, resulting mechanical strength, and air tightness were systematically investigated. The results indicated that the maximum shear strength of the joint was 34.49 MPa and leakage rate was 1.0 × 10 Pa m/s at a temperature of 495 °C for 30 min. Crystalline phases, including BiBO and BiO, were generated in the glass joint. The formation of a diffusion transition layer with a thickness of 3 μm, including elements of Al, Si, Zn, Bi, Na, and B, was the key to form an effective joint. The elements of Al, Si, and Bi had a short diffusion distance while the elements of Zn, Na, and B diffused in a long way under brazing condition.
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http://dx.doi.org/10.3390/ma13245658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764188PMC
December 2020

A multiscale coarse-grained model of the SARS-CoV-2 virion.

Biophys J 2021 03 28;120(6):1097-1104. Epub 2020 Nov 28.

Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics and James Franck Institute, The University of Chicago, Chicago, Illinois. Electronic address:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and ongoing development of a largely "bottom-up" coarse-grained (CG) model of the SARS-CoV-2 virion. Data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data become publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion.
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http://dx.doi.org/10.1016/j.bpj.2020.10.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695975PMC
March 2021

Round ligament suspending treatment in orthotopic ileal-neobladder after radical cystectomy in women: a single-centre prospective randomised trial.

BJU Int 2020 Nov 28. Epub 2020 Nov 28.

Department of Urology, Urology Institute of PLA, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Objectives: To compare the occurrence of emptying dysfunction between surgical techniques for orthotopic neobladder suspended with round ligament (rONB) and the standard procedure (sONB).

Patients And Methods: A prospective randomised controlled trial was performed in a single centre of female patients undergoing creation of an ONB using rONB or sONB. Patients were followed for ≥24 months after ONB. The primary endpoints were significant post-void residual urine volume (sPVR) and need for clean intermittent catheterisation (CIC) at 24 months postoperatively. The secondary endpoints included early and late complications, urodynamic profile, and ONB continence.

Results: Between January 2011 and October 2017, the trial enrolled 85 patients, of whom 82 were randomised. A total of 41 patients had a rONB and 41 a sONB. At 24 months, 17 of the 37 patients with a sONB and nine of the 39 patients with a rONB had a sPVR. The cumulative risk of a sPVR was significantly lower in the rONB group (23.1%) vs the sONB group (45.9%) (hazard ratio [HR] 0.43, 95% confidence interval [CI], 0.19-0.96; P = 0.040). In all, 15 of the 37 patients with a sONB and four of the 39 patients with a rONB needed CIC. The cumulative risk of requiring CIC was significantly lower in the rONB group (10.3%) vs the sONB group (40.5%) (HR 0.22, 95% CI 0.07-0.67; P = 0.008) at 24 months. Multivariable Cox regression analysis also showed that the rONB type was an independently protective factor for sPVR and CIC. The rates of early (0-90 days) and late complication (>90 days) were 54.1% and 13.5% in the sONB group, and 64.1% and 10.3% in the rONB group, respectively. There were no significant differences in complications, urodynamic profile or ONB continence. A major limitation is the small sample size at a single centre.

Conclusion: Posterior support with round ligament for an ONB significantly improved the emptying of the ONB and resulted in a reduced need for CIC. The surgical modification is a feasible and safe technique without additional complication-related surgeries.
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http://dx.doi.org/10.1111/bju.15306DOI Listing
November 2020

Imaging Cellular Aerobic Glycolysis using Carbon Dots for Early Warning of Tumorigenesis.

Adv Mater 2021 Jan 27;33(1):e2005096. Epub 2020 Nov 27.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.

Early warning of tumor formation is crucial for the classification, treatment, and prognosis of tumor patients. Here, a new strategy is reported, aimed at realizing this goal based on imaging aerobic glycolysis processes using nitrogen-doped carbon dots (N-CDs) as fluorescent probes. The intensity of the photoluminescence emitted by the N-CDs is specifically enhanced by nicotinamide adenine dinucleotide (NAD , oxidized) in the physiological environment. The N-CDs allow a few (five to ten) abnormal cells in spontaneous hepatocellular carcinoma models to be identified before the in situ development of tumor tissue. The N-CD probes can also distinguish tumor cells from normal cells and be used to evaluate their proliferation activity (with a specificity of up to 96.15% in 13 types of tumor cells and 90.90% in orthotopic xenograft models). The N-CDs are successfully used to monitor the invasion of tumor cells into neighboring tissues and body fluids in 49 clinical samples (with a sensitivity up to 79.31%). These included three vitreous body samples (from patients with retinoblastoma), 42 urine samples (22 patients clinically diagnosed with urothelium carcinoma and 20 healthy persons), and four hydrothorax samples (from patients with metastatic lesions).
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http://dx.doi.org/10.1002/adma.202005096DOI Listing
January 2021

Silencing the odorant coreceptor (Orco) disrupts sex pheromonal communication and feeding responses in Blattella germanica: toward an alternative target for controlling insect-transmitted human diseases.

Pest Manag Sci 2021 Apr 26;77(4):1674-1682. Epub 2020 Nov 26.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, P. R. China.

Background: The German cockroach, Blattella germanica, is one of the most severe pests of urban and rural areas. High-throughput genetic screening approaches indicate that the olfactory system of this pest is extremely powerful because it has an extensive array of olfactory receptor genes compared with many other insect species. Several of these genes have been identified previously, but their functions have not yet been characterized.

Results: This study describes the sequence of five transcriptomes of B. germanica adult male antennae, female antennae, maxillary palps, legs, and fifth-instar nymph antennae to investigate expression patterns of odorant receptors (ORs). Approximately 90% of ORs were found to be the most highly expressed genes in adult or nymph antennae. Additionally, every OR requires an odorant co-receptor (Orco) to become fully functional, and this was selected and successfully inhibited by injection of the corresponding double-stranded (ds)RNA targeting the Orco. A strong RNA interference (RNAi) effect was observed in which > 75% of Orco messenger RNA (mRNA) was clearly suppressed after 72 h of treatment. Olfactory behavioral assays showed that Orco-impaired B. germanica respond more slowly and show less attraction to one volatile sex pheromone and food resources compared with a control group.

Conclusion: The results show that Orco plays a pivotal role in both sex pheromone and food-seeking olfactory processes, and provide an alternative genetic technique for controlling this urban pest species by olfactory disruption. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6187DOI Listing
April 2021

Carbon-Based Quantum Dots with Solid-State Photoluminescent: Mechanism, Implementation, and Application.

Small 2020 12 3;16(48):e2004621. Epub 2020 Nov 3.

State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, CAS Center for Excellence in Superconducting Electronics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

Carbon-based quantum dots (CQDs), including spherical carbon dots and graphene quantum dots, are an emerging class of photoluminescent (PL) materials with unique properties. Great progress has been made in the design and fabrication of high-performance CQDs, however, the challenge of developing solid-state PL CQDs have aroused great interest among researchers. A clear PL mechanism is the basis for the development of high-performance solid-state CQDs for light emission and is also a prerequisite for the realization of multiple practical applications. However, the extremely complex structure of a CQD greatly limits the understanding of the solid-state PL mechanism of CQDs. So far, a variety of models have been proposed to explain the PL of solid-state CQDs, but they have not been unified. This review summarizes the current understanding of the solid-state PL of solid-state CQDs from the perspective of energy band theory and electronic transitions. In addition, the common strategies for realizing solid-state PL in CQDs are also summarized. Furthermore, the applications of CQDs in the fields of light-emitting devices, anti-counterfeiting, fingerprint detection, etc., are proposed. Finally, a brief outlook is given, highlighting current problems, and directions for development of solid-state PL of CQDs.
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http://dx.doi.org/10.1002/smll.202004621DOI Listing
December 2020

[Effect of ozone oil for prevention and treatment of sorafenib-induced hand-foot skin reactions: a randomized controlled trial].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Oct;40(10):1488-1492

Liver Cancer Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Objective: To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC).

Methods: A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group (=49) and urea ointment group (control group, =49) for treatment with local application of 1 mL medical ozone oil (experimental group) and 10% urea ointment (2 g) on the palm and plantar skin (including the fingers and joints) for 12 weeks (3 times per day) starting at the beginning of sorafenib treatment, respectively. The patients were observed for occurrence of HFSR every 2 weeks for 14 weeks.

Results: Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%; < 0.05). The incidence of grade 2/3 HFSR was also lower in ozone oil group than in urea ointment group (15.9% [7/44] 27.7 [13/47]).

Conclusions: Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.10.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606236PMC
October 2020

Increased Tumoral Microenvironmental pH Improves Cytotoxic Effect of Pharmacologic Ascorbic Acid in Castration-Resistant Prostate Cancer Cells.

Front Pharmacol 2020 23;11:570939. Epub 2020 Sep 23.

Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: The anticancer potential of pharmacologic ascorbic acid (AA) has been detected in a number of cancer cells. However, study suggested a strongly reduced cytotoxic activity of AA. It was known that pH could be a critical influencing factor for multiple anticancer treatments. In this study, we explored the influence of pH on the cytotoxicity of ascorbic acid. We employed castration-resistant prostate cancer (CRPC) cell lines PC3 and DU145 to observe the therapeutic effect of AA on PCa cells that were cultured with different pH . We also analyzed the influence of pH and extracellular oxidation on cytotoxicity of AA in cancer cells using reactive oxygen species (ROS) assay, cellular uptake of AA, and NADPH assay. Male BALB/c nude mice bearing prostate carcinoma xenografts (PC3 or DU145) were used to assess treatment response to AA with or without bicarbonate . The cellular uptake of AA in PCa xenografts was detected using positron emission tomography (PET). Small animal PET/CT scans were performed on mice after the administration of 6-deoxy-6-[F] fluoro-L-ascorbic acid (F-DFA).

Results: Our studies demonstrate that acidic pH attenuates the cytotoxic activity of pharmacologic ascorbic acid by inhibiting AA uptake in PCa cells. Additionally, we found that the cancer cell-selective toxicity of AA depends on ROS. , combination of AA and bicarbonate could provide a significant better therapeutic outcome in comparison with controls or AA single treated mice. F-DFA PET imaging illustrated that the treatment with NaHCO could significantly increase the AA uptake in tumor.

Conclusions: The alkalinity of tumor microenvironment plays an important role in anticancer efficiency of AA in CRPC. F-DFA PET/CT imaging could predict the therapeutic response of PCa animal model through illustration of tumoral uptake of AA. F-DFA might be a potential PET tracer in clinical diagnosis and treatment for CRPC.
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http://dx.doi.org/10.3389/fphar.2020.570939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538777PMC
September 2020