Publications by authors named "Feifei Wang"

414 Publications

Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer.

Cell Death Dis 2021 May 13;12(5):484. Epub 2021 May 13.

Department of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangzhou, 510515,, Guangdong Province, People's Republic of China.

In colorectal cancer (CRC), overt metastases often appear after years of latency. But the signals that cause micro-metastatic cells to remain indolent, thereby enabling them to survive for extended periods of time, are unclear. Immunofluorescence and co-immunoprecipitation assays were used to explore the co-localization of CCL7 and CCR2. Immunohistochemical (IHC) assays were employed to detect the characters of metastatic HT29 cells in mice liver. Flow cytometry assays were performed to detect the immune cells. Bruberin vivo MS FX Pro Imager was used to observe the liver metastasis of CRC in mice. Quantitative real-time PCR (qRT-PCR) and western blot were employed to detect the expressions of related proteins. Trace RNA sequencing was employed to identify differentially expressed genes in MDSCs from liver micro-M and macro-M of CRC in mice. Here, we firstly constructed the vitro dormant cell models and metastatic dormant animal models of colorectal cancer. Then we found that myeloid-derived suppressor cells (MDSCs) were increased significantly from liver micro-metastases to macro-metastases of CRC in mice. Moreover, monocytic MDSCs (Mo-MDSC) significantly promoted the dormant activation of micro-metastatic cells compared to polymorphonuclear MDSCs (PMN-MDSC). Mechanistically, CCL7 secreted by Mo-MDSCs bound with membrane protein CCR2 of micro-metastatic cells and then stimulated the JAK/STAT3 pathway to activate the dormant cells. Low-dose administration of CCL7 and MDSCs inhibitors in vivo could significantly maintain the CRC metastatic cells dormant status for a long time to reduce metastasis or recurrence after radical operation. Clinically, the level of CCL7 in blood was positively related to the number of Mo-MDSCs in CCR patients, and highly linked with the short-time recurrence and distant metastasis. CCL7 secreted by Mo-MDSCs plays an important role in initiating the outgrowth of metastatic latent CRC cells. Inhibition of CCL7 might provide a potential therapeutic strategy for the prevention of metastasis recurrence.
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http://dx.doi.org/10.1038/s41419-021-03698-5DOI Listing
May 2021

Dimeric Her2-specific affibody mediated cisplatin-loaded nanoparticles for tumor enhanced chemo-radiotherapy.

J Nanobiotechnology 2021 May 13;19(1):138. Epub 2021 May 13.

Department of Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.

Background: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy.

Results: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (Z) mediated cisplatin-loaded mesoporous polydopamine/MnO/polydopamine nanoparticles (Pt@mPDA/MnO/PDA-Z NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O. Z, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of Z. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization.

Conclusions: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.
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http://dx.doi.org/10.1186/s12951-021-00885-6DOI Listing
May 2021

Transverse distribution of the streamwise velocity for the open-channel flow with floating vegetated islands.

Environ Sci Pollut Res Int 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, Wuhan, 430072, Hubei, China.

Floating vegetation islands (FVIs) have been widely utilized in various river ecological restoration projects due to their ability to purify pollutants. FVIs float at the surface of shallow pools with their roots unanchored in the sediment. Biofilm formed by roots under islands filters nutrients and particles in the water flowing through it. Flow field disturbance will occur, and transverse distribution of flow velocity will change due to the existence of FVIs. Transport efficiency of suspended solids, nutrients, and pollutants will also be altered. A modified analytical model that considers the effects of boundary friction, drag force of vegetation, transverse shear turbulence, and secondary flow is established to model the transverse distributions of depth-averaged streamwise velocity for the open-channel flow with FVIs using the Shiono and Knight Method. The simulation results with suitable boundary conditions successfully modeled the lateral profile of the depth-averaged streamwise velocity compared with the experimental results of symmetrical and unsymmetrical arrangements of FVIs. Hence, the presented model is of guiding significance to investigate the flow characteristics of rivers with FVIs.
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http://dx.doi.org/10.1007/s11356-021-14353-zDOI Listing
May 2021

Desmoplastic Small Round Cell Tumor of the Kidney with Mainly Pulmonary Symptoms by F-FDG PET/CT.

Urology 2021 May 5. Epub 2021 May 5.

Department of Nuclear Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, PR China. 646000; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, PR China. 646000; Academician (Expert) Workstation of Sichuan Province. Electronic address:

Desmoplastic small round cell tumor (DSRCT) is a rare malignancy believed to originate from the serous membranes and it is highly aggressive with 5-year overall survival of 18.4%. Only a small number of DSRCT cases have been documented. Here, we report findings of DSRCT of the kidney on F-FDG PET/CT in a 30-year-old woman who presented with repetitive pulmonary infection and spontaneous pneumothorax.
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http://dx.doi.org/10.1016/j.urology.2021.04.026DOI Listing
May 2021

Ultrafast optical response and ablation mechanisms of molybdenum disulfide under intense femtosecond laser irradiation.

Light Sci Appl 2020 May 6;9(1):80. Epub 2020 May 6.

Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.

Numerous valuable studies on electron dynamics have focussed on the extraordinary properties of molybdenum disulfide (MoS); however, most of them were confined to the level below the damage threshold. Here the electron dynamics of MoS under intense ultrafast laser irradiation was investigated by experiments and simulations. Two kinds of ablation mechanisms were revealed, which led to two distinct types of electron dynamics and final ablation morphology. At a higher fluence, the emergence of superheated liquid induced a dramatic change in the transient reflectivity and micro-honeycomb structures. At a lower fluence, the material was just removed by sublimation, and the ablation structure was relatively flat. X-ray photoelectron spectroscopic (XPS) measurements demonstrated that thermal decomposition only occurred at the higher fluence. Furthermore, a theoretical model was developed to deeply reveal the ultrafast dynamics of MoS ablation. The simulation results were in good agreement with the temporal and spatial reflectivity distribution obtained from the experiment. The electron and lattice temperature evolution was also obtained to prove the ablation mechanism. Our results revealed ultrafast dynamics of MoS above the damage threshold and are helpful for understanding the interaction mechanism between MoS and intense ultrafast lasers, as well as for MoS processing applications.
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http://dx.doi.org/10.1038/s41377-020-0318-8DOI Listing
May 2020

Nasal nitric oxide testing for allergic rhinitis patients: Systematic review and meta-analysis.

Immun Inflamm Dis 2021 May 5. Epub 2021 May 5.

Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Background: Nasal nitric oxide (nNO) levels in allergic rhinitis (AR), healthy people or nonallergic rhinitis (NAR) have shown contradicting results in previous studies. By meta-analysis, we reviewed studies that measured nNO in AR patients to assess nNO's ability to discriminate AR from healthy people or NAR.

Methods: We systematically searched PubMed, Cochrane, Embase, Ovid, Web of Science, Wanfang Data, CNKI until December 15, 2020. Differences were expressed as standardized mean differences (SMD) with 95% confidence interval (CI), by random-effects method.

Results: A total of 10 original studies with 561 AR patients, 327 healthy controls, 123 NAR patients were included in the narrative synthesis and 9 studies in the meta-analysis. nNO in AR was significantly increased compared with healthy controls (SMD: 0.989; 95% CI: 0.402, 1.576; p = .001) or NAR (SMD: 0.680; 95% CI: 0.101, 1.259; p = 0.021). However, subgroup analysis based on measuring process and patient characteristics showed that no significant differences were detected in nNO between AR patients with nasal polyps or sinusitis or marked ostial obstruction and healthy controls.

Conclusions: nNO is a potential indicator for recognizing AR. Nasal polyps, sinusitis and marked ostial obstruction should be considered before nNO is applied to detect AR.
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http://dx.doi.org/10.1002/iid3.439DOI Listing
May 2021

Association between potentially inappropriate medication and adverse drug reactions in hospitalized elderly patients.

J Clin Pharm Ther 2021 Apr 27. Epub 2021 Apr 27.

Pharmacy Department of Hefei BOE Hospital, Hefei, P. R. China.

What Is Known And Objective: The Beers, European Union (EU) and Screening Tool of Older Persons' potentially inappropriate Prescription (STOPP) criteria were developed to improve the safe use of medicines in the elderly. However, the predictive validity of existing criteria to detect adverse drug reactions (ADRs) remains unexplored. The objective of the current study was to determine whether the 2019 Beers, 2015 STOPP or 2015 EU potentially inappropriate medicine (PIM) criteria were associated with ADRs.

Methods: A retrospective, cross-sectional investigation was conducted among older persons (≥60 years of age) admitted to a tertiary hospital in China between April 2019 and December 2019. PIMs were identified as per the Beers, EU and STOPP criteria definitions. ADRs were retrospectively evaluated by two clinical pharmacists using the Naranjo algorithm. Multivariate logistic regression was used to evaluate the factors associated with ADRs in the hospitalized patients.

Results And Discussion: The study participants included 560 hospitalized patients (mean age 72.05 ± 8.15). The prevalence of patients receiving at least one PIM was 52.1%, 37.0% and 42.9% according to the Beers, EU and STOPP criteria, respectively. Univariate analysis showed that ADRs were associated with PIMs listed in the Beers criteria (OR: 2.093, 95% CI: 1.028-4.263, 0.042), but not with the STOPP-listed (OR: 0.536, 95% CI: 0.255-1.123, 0.098) and EU-listed PIMs (OR: 0.258, 95% CI: 0.118-0.563, 0.001).

What Is New And Conclusion: In contrast to the STOPP and EU criteria on PIMs, the Beers criteria were significantly associated with avoidable ADRs in hospitalized older persons.
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http://dx.doi.org/10.1111/jcpt.13413DOI Listing
April 2021

miR-151 Affects Low-Temperature Tolerance of by Modulating Autophagy Under Low-Temperature Stress.

Front Cell Dev Biol 2021 9;9:595108. Epub 2021 Apr 9.

Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, Key Laboratory of Ecology and Environmental Science in Guangdong Higher Education, College of Life Sciences, South China Normal University, Guangzhou, China.

MicroRNAs (miRNAs) play key roles in many physiologic and pathologic processes, including autophagy. Autophagy is cellular in an emergency response mechanism of environment stress, but their complex molecular regulatory mechanism under low-temperature stress is largely unknown in shrimp, especially miRNA-mediated regulation of autophagy in low-temperature tolerance. In this article, a shrimp and miRNA pva-miR-151 cooperation in response to low-temperature stress has been reported. Pva-miR-151 showed expression patterns opposite to target under low-temperature stress. The pva-miR-151 targets the 3'-UTR region of , regulate the formation of autophagosome, which contribute to the degradation and recycling of damaged organelles. In addition, the low-temperature tolerance was correlated positively with autophagy in shrimp. Silenced pva-miR-151 increased sensitivity to low-temperature stress, whereas overexpression pva-miR-151 decreased the expression of PvTOR and p-TOR and increased tolerance to low-temperature stress by improving the formation of autophagosome and total hemocyte count. In addition, the TOR activator 3BDO can partially rescue autophagy induced by overexpression of pva-miR-151; these results indicate that miR-151 was necessary for the low-temperature tolerance in shrimp. Taken together, we provide a novel strategy and mechanism for shrimp breeding to improve shrimp low-temperature tolerance.
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http://dx.doi.org/10.3389/fcell.2021.595108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064728PMC
April 2021

Respiratory diseases are positively associated with PM2.5 concentrations in different areas of Taiwan.

PLoS One 2021 22;16(4):e0249694. Epub 2021 Apr 22.

College of Management, Fu Jen Catholic University, Taipei, Taiwan.

The health effects associated with fine particulate matter (PM2.5) have attracted considerable public attention in recent decades. It has been verified that PM2.5 can damage the respiratory and cardiovascular systems and cause various diseases. While the association between diseases and PM2.5 has been widely studied, this work aims to analyze the association between PM2.5 and hospital visit rates for respiratory diseases in Taiwan. To this end, a disease mapping model that considers spatial effects is applied to estimate the association. The results show that there is a positive association between hospital visit rates and the PM2.5 concentrations in the Taiwanese population in 2012 after controlling for other variables, such as smoking rates and the number of hospitals in each region. This finding indicates that control of PM2.5 could decrease hospital visit rates for respiratory diseases in Taiwan.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249694PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062073PMC
April 2021

Visible/near-infrared light absorbed nano-ferroelectric for efficient photo-piezocatalytic water splitting and pollutants degradation.

J Hazard Mater 2021 Apr 6;416:125808. Epub 2021 Apr 6.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

The band structure of ferroelectrics can be modulated by mechanical stress induced piezoelectric polarization charges, and thus to promote the separation of photo-excited carriers, endowing photo-piezocatalysts with good performance in hydrogen production and pollutants degradation. However, the catalytic performance of these conventional photo-piezocatalysts is restricted since they mainly harvest UV light and generally have limited piezoelectricity. Here, in this study, by using self-propagation high-temperature synthesis process, highly piezoelectric gap-state-engineered nano relaxor ferroelectric at the morphotropic phase boundary, such as (NaBi)TiO-Ba(TiNi)O is synthesized for the first time and shows unprecedently light harvesting from UV to near-infrared (λ < 1300 nm). We demonstrate a significantly enhanced photo-piezocatalytic performance for this photo-piezocatalyst. A high hydrogen production rate of ~ 450 μmol g h is obtained and the decomposition of Rhodamine B dye is nearly completed after 20 min under irradiation and ultrasonic vibration. Moreover, an unprecedently efficient NIR-driven photocatalytic degradation of RhB is also demonstrated by using photo-piezocatalysts. This kind of novel multifunctional nano photo-piezocatalysts opens up new horizons to all-day available photo-piezocatalytic technology for a more efficient use of multisource energies from environment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125808DOI Listing
April 2021

ZnO/CPAN Modified Contact Lens with Antibacterial and Harmful Light Reduction Capabilities.

Adv Healthc Mater 2021 Apr 19:e2100259. Epub 2021 Apr 19.

College of Chemistry, Nanchang University, Nanchang, Jiangxi, 330088, China.

Compared with traditional glasses, the comfortable and convenient contact lens (CL) has seen an upsurge among the public. However, due to the lack of antibacterial properties of ordinary CLs, the risk of eye infection is greatly increased accordingly. On the other hand, ordinary CLs also cannot effectively reduce the short-wavelength blue light emitted from electronic products, such as mobile phones and computers. Aiming at the above two problems, zinc oxide (ZnO)/cyclized polyacrylonitrile (CPAN) composites are developed for CL modification. After loading with ZnO/CPAN (ZC), the CL shows a broad-spectrum antibacterial property. Further experiments also prove that it can block UVB, UVA, as well as blue light selectively, under the premise of ensuring hydrophilicity and certain transparency. Theoretically, this ZC-decorated CL can fundamentally reduce the damage to the eyes from harmful light emitted by light-emitting diodes and the secretion of pro-inflammatory factors, which is thus a promising eye protection strategy for modern society.
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http://dx.doi.org/10.1002/adhm.202100259DOI Listing
April 2021

TREM2 Dictates Antibacterial Defense and Viability of Bone Marrow-derived Macrophages During Bacterial Infection.

Am J Respir Cell Mol Biol 2021 Apr 13. Epub 2021 Apr 13.

Zhejiang University School of Medicine First Affiliated Hospital, 71069, Anesthesiology and Intensive Care, Hangzhou, China;

Macrophages undergo profound metabolic reprogramming to join key immunoregulatory functions, which can be initiated by pattern recognition receptors. TREM2, a macrophage phagocytic receptor, plays pivotal roles in sepsis by enhancing bacterial clearance, which is associated with regulation of reactive oxygen species (ROS) production. However, how intracellular ROS participate in TREM2-mediated bactericidal activity remains unclear. This study was designed to investigate the organelle source and biological activity of ROS in the context of TREM2-mediated immune defense during E.coli infection. Bone marrow-derived macrophages (BMDMs) were transfected with TREM2-overexpressing adenoviruses or control viruses, and challenged with E.coli. The BMDMs were administered to mouse models with local E.coli infection. Additionally, monocytic TREM2 expression, NOX2 levels and pyroptosis were detected in patients with bacterial sepsis. General ROS production was found to be comparable between TREM2-overexpressing and control BMDMs upon E.coli challenge. The deficiency of Nox2 led to impaired phagosome degradation and lack of bactericidal ability and abolished TREM2-mediated protective activity against pulmonary E.coli infection. Overexpression of TREM2 suppressed mitochondrial ROS generation, inhibited NLRP3/caspase-1 inflammasome activation, and finally protected BMDMs from gasdermin D-mediated pyroptosis during pulmonary E.coli infection. The protective role of TREM2 was further confirmed in mice with abdominal E.coli infection. Moreover, monocytic TREM2 expression was positively correlated with NOX2 levels and negatively correlated with pyroptosis and disease severity in patients with bacterial sepsis. Collectively, TREM2 controls macrophage immune functions by fine-tuning ROS generation and enhances the host defense against bacterial infection. Our data suggest that TREM2 is a promising candidate target for sepsis therapy.
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http://dx.doi.org/10.1165/rcmb.2020-0521OCDOI Listing
April 2021

Thiophene donor for NIR-II fluorescence imaging-guided photothermal/photodynamic/chemo combination therapy.

Acta Biomater 2021 Apr 6. Epub 2021 Apr 6.

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA. Electronic address:

Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared (NIR-I) window. However, their applications in the second near-infrared (NIR-II) window are still limited primarily due to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) is created as a molecularly engineered thiophene donor unit with high QYs to the redshift. Thiophene insertion initiates substantial redshifts of the absorbance as compared to its counterparts in which iodine is introduced. The fluorescent molecule can be triggered by an NIR laser with a single wavelength, thereby producing emission in the NIR-II windows. Single NIR laser-triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and the chemotherapeutic drug docetaxel (DTX) by using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen QY (Φ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics. After intravenous administration of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor showed a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the combination of photodynamic therapy (PDT) and photothermic therapy (PTT). STATEMENT OF SIGNIFICANCE: The application of organic photosensitizers is still limited primarily due to low fluorescence quantum yields (QYs) in the second near-infrared (NIR-II) window. Here, a boron dipyrromethene (BDP) as a molecularly engineered thiophene donor unit with high QYs to the redshift is created. Phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and docetaxel (DTX) using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show high singlet oxygen QY (Φ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics and a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the PDT/PTT combination therapy.
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http://dx.doi.org/10.1016/j.actbio.2021.03.064DOI Listing
April 2021

Direct observation of nanoscale dynamics of ferroelectric degradation.

Nat Commun 2021 Apr 7;12(1):2095. Epub 2021 Apr 7.

School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW, Australia.

Failure of polarization reversal, i.e., ferroelectric degradation, induced by cyclic electric loadings in ferroelectric materials, has been a long-standing challenge that negatively impacts the application of ferroelectrics in devices where reliability is critical. It is generally believed that space charges or injected charges dominate the ferroelectric degradation. However, the physics behind the phenomenon remains unclear. Here, using in-situ biasing transmission electron microscopy, we discover change of charge distribution in thin ferroelectrics during cyclic electric loadings. Charge accumulation at domain walls is the main reason of the formation of c domains, which are less responsive to the applied electric field. The rapid growth of the frozen c domains leads to the ferroelectric degradation. This finding gives insights into the nature of ferroelectric degradation in nanodevices, and reveals the role of the injected charges in polarization reversal.
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http://dx.doi.org/10.1038/s41467-021-22355-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027400PMC
April 2021

Mediastinum-type lung cancer on 68Ga-FAPI PET/CT with cardiac insufficiency as the first symptom.

J Nucl Cardiol 2021 Apr 6. Epub 2021 Apr 6.

Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, No 15 TaiPing St, Jiangyang District, Luzhou, 646000, Sichuan, People's Republic of China.

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http://dx.doi.org/10.1007/s12350-021-02601-1DOI Listing
April 2021

CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer.

Cancer Immunol Immunother 2021 Apr 5. Epub 2021 Apr 5.

Department of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China.

Background: CMTM6 is a novel key regulator of PD-L1. High expression of both CMTM6 and PD-L1 may predict the benefit of PD-1 axis blockade in lung cancer. We aimed to investigate the expression pattern of CMTM6 between mismatch repair-defective (dMMR) and mismatch repair-proficient (pMMR) colorectal cancer (CRC) tissues and assess its correlation with the response to PD-1/PD-L1 pathway blockade.

Methods: Immunohistochemistry (IHC) was used to analyze CMTM6 and PD-L1 expression and immune cell density in dMMR/pMMR CRC. Quantitative multiplex immunofluorescence (IF) was performed to detect CMTM6, PD-L1, CD4, CD8, CD68 and CD163 expression in CRC patients treated with PD-1/PD-L1 inhibitors.

Result: IHC analysis showed that CMTM6 and PD-L1 were both expressed in tumor cells (TCs) and invasion front immune cells (ICs). CMTM6 and PD-L1 expression and CD4, CD8, CD68 or CD163 cell density were significantly higher in dMMR CRC patients than in pMMR CRC patients. CMTM6 expression was positively correlated with PD-L1 expression and CD163 M2 macrophage density in dMMR CRC. IF analysis showed that the coexpression rate of CMTM6/PD-L1 and the expression rate of CMTM6 in CD8 T cells and CD163 M2 macrophages were significantly increased in the group that exhibited clinical benefit. CMTM6 expression in M2 macrophages was identified as the best biomarker for predicting the responsiveness to PD-1/PD-L1 inhibitors.

Conclusions: CMTM6 expression in M2 macrophages may predict the PD-1/PD-L1 inhibitor response rate in CRC patients more accurately than dMMR/microsatellite instability-high (MSI-H) status. It can also identify pMMR CRC patients who could benefit from PD-1/PD-L1 inhibitors.
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http://dx.doi.org/10.1007/s00262-021-02931-6DOI Listing
April 2021

Restraint Stress in Hypertensive Rats Activates the Intestinal Macrophages and Reduces Intestinal Barrier Accompanied by Intestinal Flora Dysbiosis.

J Inflamm Res 2021 25;14:1085-1110. Epub 2021 Mar 25.

Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing, 100069, People's Republic of China.

Purpose: Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels.

Methods: Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing.

Results: The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (Mφ) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio.

Conclusion: Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.
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http://dx.doi.org/10.2147/JIR.S294630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007621PMC
March 2021

Confocal laser endomicroscopy under propofol-based sedation for early gastric cancer and pre-cancerous lesions is associated with better diagnostic accuracy: a retrospective cohort study in China.

BMC Anesthesiol 2021 Mar 30;21(1):97. Epub 2021 Mar 30.

Department of Anesthesiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, Hangzhou, China.

Background: Confocal laser endomicroscopy (CLE) has advantages in detecting gastric neoplastic lesions, meanwhile it requires strict patient cooperation. Sedation could improve patient cooperation and quality of endoscopy. However, sedation is still not very popular in some resource-limited countries and regions. The purpose of this study was to compare propofol-based sedated versus un-sedated CLE in the value of diagnosing early gastric cancer (EGC) and precancerous lesions.

Methods: A retrospective, cohort, single center study of 226 patients who underwent CLE between January 1, 2015 and December 31, 2017 was performed. Patients enrolled were allocated into the propofol-based sedated group (n = 126) and the un-sedated group (n = 100). The comparison of validity and reliability of CLE for identifying EGC and precancerous lesions between the two groups was performed through analyzing CLE diagnosis and pathological diagnosis. Reporting followed the STROBE guidelines.

Results: The area under receiver operating characteristic curve (AUROC) of diagnosing EGC in the sedated group was 0.97 (95 % CI: 0.95 to 0.99), which was higher than that in the un-sedated group (0.88 (95 % CI: 0.80 to 0.97), P = 0.0407). CLE with sedation performed better than without sedation in diagnosing intraepithelial neoplasia and intestinal metaplasia (P = 0.0008 and P = 0.0001, respectively). For patients considered as high-grade intraepithelial neoplasia or EGC by endoscopists, they would not get biopsy during CLE but receive endoscopic submucosal dissection (ESD) subsequently, and the misdiagnosis rate of CLE was 0 % in the sedated group and 27.59 % (95 % CI: 10.30-44.91 %) in the un-sedated group (P = 0.006).

Conclusions: Propofol based sedation was associated with improved diagnostic value of CLE for detecting EGC as well as precancerous lesions (intraepithelial neoplasia OR intestinal metaplasia).
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http://dx.doi.org/10.1186/s12871-021-01312-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008607PMC
March 2021

Physicochemical Characteristics of Cellulose Nanocrystals Derived from the Residue of Filamentous Microalga Tribonema utriculosum.

Appl Biochem Biotechnol 2021 Mar 12. Epub 2021 Mar 12.

Institute of Hydrobiology, Department of Ecology, Jinan University, Guangzhou, 510632, People's Republic of China.

Tribonema biomass is considered promising biorefinery feedstock for the co-production of biodiesel and valuable bioproducts; however, the extraction of these useful compounds produces large amounts of algal residues, which produce increased environmental concerns. Herein, cellulose was extracted from the waste residue of T. utriculosum via alkalization and bleaching, followed by the production of high-value-added cellulose nanocrystals (CNCs) via acid hydrolysis. The hydrolysis was performed with 60% (wt%) HSO at a yield of 13.31%, resulting in the generation of rod-shaped nanoparticles averaging 39.5 nm in diameter and 239.2 nm in length. The structural characterization analysis revealed that the prepared CNCs had high crystallinity (73.0%) due to the removal of non-cellulose components and amorphous regions by chemical treatment, as well as possessing good aqueous suspension stability (zeta potential = - 40.1 mV). Although the CNCs showed lower thermal stability than extracted cellulose, they spanned a broader temperature range due to two-stage degradation behaviour, with higher residue weight (16.7%). This work represents the first report on the preparation of a high-value-added industrial product, CNCs, from the filamentous microalga T. utriculosum, aiming to maximize benefits from waste algal residue reutilization.
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http://dx.doi.org/10.1007/s12010-021-03495-yDOI Listing
March 2021

Antioxidant Enzymatic Activity and Osmotic Adjustment as Components of the Drought Tolerance Mechanism in .

Plants (Basel) 2021 Feb 25;10(3). Epub 2021 Feb 25.

Beijing Research Center of Intelligent Equipment for Agriculture, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.

Drought stress is a major environmental constraint for plant growth. Climate-change-driven increases in ambient temperatures resulted in reduced or unevenly distributed rainfalls, leading to increased soil drought. C. A. Mey is a typical drought-tolerant sedge, but few reports have examined the mechanisms conferring its tolerant traits. In the present study, the drought responses of were assessed by quantifying activity of antioxidant enzymes in its leaf and root tissues and evaluating the relative contribution of organic and inorganic osmolyte in plant osmotic adjustment, linking it with the patterns of the ion acquisition by roots. Two levels of stress-mild (MD) and severe (SD) drought treatments-were used, followed by re-watering. Drought stress caused reduction in a relative water content and chlorophyll content of leaves; this was accompanied by an increase in the hydrogen peroxide (HO) and superoxide (O) contents in leaves and roots. Under MD stress, the activities of catalase (CAT), peroxidase (POD), and glutathione peroxidase (GPX) increased in leaves, whereas, in roots, only CAT and POD activities increased. SD stress led to an increase in the activities of CAT, POD, superoxide dismutase (SOD), and GPX in both tissues. The levels of proline, soluble sugars, and soluble proteins in the leaves also increased. Under both MD and SD stress conditions, increased K, Na, and Cl uptake by plant roots, which resulted in an increased K, Na, and Cl concentrations in leaves and roots. This reliance on inorganic osmolytes enables a cost-efficient osmotic adjustment in . Overall, this study revealed that was able to survive arid environments due to an efficient operation of its ROS-scavenging systems and osmotic adjustment mechanisms.
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http://dx.doi.org/10.3390/plants10030436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996351PMC
February 2021

Efficient degradation of Congo red and phenol by a new photocatalyst Ag/AgBr-Al-attapulgite composite under visible light irradiation.

Environ Sci Pollut Res Int 2021 Feb 27. Epub 2021 Feb 27.

School of Environmental and Chemical Engineering, Shanghai University, Shangda Road 99, Shanghai, 200444, China.

Nowadays the concern on the treatment of refractory organic pollutants (e.g., Congo red and phenolic compounds) in industrial wastewaters and their treated effluents with conventional technologies has been still continuously increasing. In this study, a novel visible light photocatalyst material, Ag/AgBr and Al loading on the attapulgite (ATP), was prepared for efficiently catalyzing the photodegradation of the two refractory substances, and its photocatalytic performance and recyclability were assessed. Results from transmission electron microscopy and X-ray diffraction confirmed the successful loading of Ag/AgBr and Al on the ATP. The prepared Ag/AgBr-Al-ATP composite presented substantially better catalytic performance than Ag/AgBr alone probably because the ATP as a carrier of catalyst provided more contact surface for catalyst Ag/AgBr and Congo red/phenol. In the Ag/AgBr-Al-ATP composite, the photocatalyst AgBr content increased from 20.4 to 34.9% due to the modification of ATP by Al. Correspondingly, the Ag/AgBr-Al-ATP composite presented its excellent photocatalytic performance under visible light irradiation: photodegradation efficiencies of Congo red and phenol of 1.73 mg/100 mg and 0.86 mg/100 mg were achieved. With the increase of pH, the photolysis efficiencies of Congo red and phenol both first increased and then decreased, whereas the optimal photocatalytic performance occurred at pH 7 for Congo red and pH 10 for phenol. The Ag/AgBr-Al composite presented a high catalytic activity for photolysis of Congo red and phenol in all the four consecutive reused cycles. The results in this study comprehensively demonstrated a promising photocatalyst for efficient removal of the similar refractory organics presented in industrial wastewaters, which deserves further investigation and development.
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http://dx.doi.org/10.1007/s11356-021-12737-9DOI Listing
February 2021

Cancer theranostic platforms based on injectable polymer hydrogels.

Biomater Sci 2021 Feb 26. Epub 2021 Feb 26.

Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.

Theranostic platforms that combine therapy with diagnosis not only prevent the undesirable biological responses that may occur when these processes are conducted separately, but also allow individualized therapies for patients. Polymer hydrogels have been employed to provide well-controlled drug release and targeted therapy in theranostics, where injectable hydrogels enable non-invasive treatment and monitoring with a single injection, offering greater patient comfort and efficient therapy. Efforts have been focused on applying injectable polymer hydrogels in theranostic research and clinical use. This review highlights recent progress in the design of injectable polymer hydrogels for cancer theranostics, particularly focusing on the elements/components of theranostic hydrogels, and their cross-linking strategies, structures, and performance with regard to drug delivery/tracking. Therapeutic agents and tracking modalities that are essential components of the theranostic platforms are introduced, and the design strategies, properties and applications of the injectable hydrogels developed via two approaches, namely chemical bonds and physical interactions, are described. The theranostic functions of the platforms are highly dependent on the architecture and components employed for the construction of hydrogels. Challenges currently presented by theranostic platforms based on injectable hydrogels are identified, and prospects of acquiring more comfortable and personalized therapies are proposed.
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http://dx.doi.org/10.1039/d0bm02149kDOI Listing
February 2021

Air quality characteristics in Wuhan (China) during the 2020 COVID-19 pandemic.

Environ Res 2021 04 17;195:110879. Epub 2021 Feb 17.

School of Environmental Science & Engineering, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, PR China.

Understanding the relationship between air quality, pollution emission control measures, and meteorological conditions is important for developing effective air quality improvement policies. In this study, we used pollution monitoring and meteorological data from January to May 2020 to analyze the air quality characteristics during the COVID-19 lockdown in Wuhan, which lasted from January 23 to April 8, 2020. Compared with the same period in 2019, the air quality in 2020 was significantly better. The total excellent and good air quality rates increased by 17.58%-90.08% in 2020; concentrations of NO, particulate matter with a diameter <10 μm (PM) and <2.5 μm (PM), and total volatile organic compounds (TVOCs) also decreased by 38.23%, 30.25%, 32.92%, and 39.80%, respectively. Moreover, the number of days with NO, PM, and PM as the primary pollutants decreased by approximately 10%, 9%, and 15%, respectively. We compared the wind direction, wind speed, temperature, and relative humidity in January-April 2020, 2019, 2018, and 2017 and found no obvious correlation between meteorological factors and improved air quality during the 2020 lockdown. The implementation of strict lockdown measures, such as home quarantining, traffic restrictions, and non-essential enterprise shutdowns, was the dominant cause for the substantial air quality improvement during the 2020 COVID-19 lockdown in Wuhan.
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http://dx.doi.org/10.1016/j.envres.2021.110879DOI Listing
April 2021

One-Step Fabrication Method of GaN Films for Internal Quantum Efficiency Enhancement and Their Ultrafast Mechanism Investigation.

ACS Appl Mater Interfaces 2021 Feb 8;13(6):7688-7697. Epub 2021 Feb 8.

Laser Assisted Nano Engineering Laboratory, Department of Electrical Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0511, United States.

The third-generation semiconductors are the cornerstone of the power semiconductor leap forward and have attracted much attention because of their excellent properties and wide applications. Meanwhile, femtosecond laser processing as a convenient method further improves the performance of the related devices and expands the application prospect. In this work, an approximate 3 times improvement of the internal quantum efficiency (IQE) and a 5.5 times enhancement of the photoluminescence (PL) intensity were achieved in the GaN film prepared using a one-step femtosecond laser fabrication method. Three types of final micro/nanostructures were found with different femtosecond laser fluences, which could be attributed to the decomposition, melting, bubble nucleation, and phase explosion of GaN. The mechanisms of the microbump structure formation and enhancement of IQE were studied experimentally by the time-resolved reflection pump-probe technique, X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Simulations for the laser-GaN interaction have also been performed to ascertain the micro/nanostructure formation principle. These results promote the potential applications of femtosecond lasers on GaN and other wide band gap semiconductors, such as UV-light-emitting diodes (LEDs), photodetectors, and random lasers for use in sensing and full-field imaging.
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http://dx.doi.org/10.1021/acsami.0c19726DOI Listing
February 2021

In vivo NIR-II structured-illumination light-sheet microscopy.

Proc Natl Acad Sci U S A 2021 Feb;118(6)

Department of Chemistry, Stanford University, Stanford, CA 94305;

Noninvasive optical imaging with deep tissue penetration depth and high spatiotemporal resolution is important to longitudinally studying the biology at the single-cell level in live mammals, but has been challenging due to light scattering. Here, we developed near-infrared II (NIR-II) (1,000 to 1,700 nm) structured-illumination light-sheet microscopy (NIR-II SIM) with ultralong excitation and emission wavelengths up to ∼1,540 and ∼1,700 nm, respectively, suppressing light scattering to afford large volumetric three-dimensional (3D) imaging of tissues with deep-axial penetration depths. Integrating structured illumination into NIR-II light-sheet microscopy further diminished background and improved spatial resolution by approximately twofold. In vivo oblique NIR-II SIM was performed noninvasively for 3D volumetric multiplexed molecular imaging of the CT26 tumor microenvironment in mice, longitudinally mapping out CD4, CD8, and OX40 at the single-cell level in response to immunotherapy by cytosine-phosphate-guanine (CpG), a Toll-like receptor 9 (TLR-9) agonist combined with OX40 antibody treatment. NIR-II SIM affords an additional tool for noninvasive volumetric molecular imaging of immune cells in live mammals.
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http://dx.doi.org/10.1073/pnas.2023888118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017937PMC
February 2021

Effect of oxidation ditch and anaerobic-anoxic-oxic processes on CXR-type disinfection by-product formation during wastewater treatment.

Sci Total Environ 2021 May 22;770:145344. Epub 2021 Jan 22.

State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

The high chlorine dosages in wastewater treatment plants during the COVID-19 pandemic may result in increased formation of disinfection by-products (DBPs), posing great threat to the aquatic ecosystem of the receiving water body and the public health in the downstream area. However, limited information is available on the effect of biological wastewater treatment processes on the formation of CXR-type DBPs. This study investigated the effect of oxidation ditch (OD) and anaerobic-anoxic-oxic (AAO), two widely used biological wastewater treatment processes, on the formation of five classes of CXR-type DBPs, including trihalomethanes (THMs), haloacetic acids (HAAs), haloacetaldehydes (HALs), haloacetonitriles (HANs) and halonitromethanes (HNMs), during chlorination. Experimental results showed that biological treatment effectively reduced the dissolved organic carbon (DOC) and UV, while it increased the dissolved organic nitrogen (DON), and therefore the ratio of DON/DOC. In addition, increases in the contents of soluble microbial product- and humic acid-like matters, and the transformation of high molecular weight (MW) fractions in the dissolved organic matter into low MW fractions were observed after OD and AAO processes. Although biological treatment effectively decreased the formation of Cl-THMs, Cl-HAAs, Cl-HANs and Cl-HNMs, the formation of DBCM, DBAA, BDCAA, DBCAA, DCAL, TCAL and DBAN (where C = chloro, B = bromo, D = di, T = tri) all increased significantly, due to the increased formation reactivity. Moreover, biological treatment increased the ratio of bromide/DOC and bromine incorporation into THMs, HAAs and DHANs except for HALs and THANs. Different from previous studies, this study revealed that biological treatment increased the formation of some DBPs, especially brominated DBPs, despite the efficient removal of organic matters. It provides insights into the DBP risk control in wastewater treatment, particularly during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145344DOI Listing
May 2021

Application of three-dimensional reconstruction with a Hisense computer-assisted system in upper pancreatic lymph node dissection during laparoscopic-assisted radical gastrectomy.

Asian J Surg 2021 May 23;44(5):730-737. Epub 2021 Jan 23.

General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. Electronic address:

Background/objective: To investigate the feasibility of three-dimensional (3D) reconstruction with an interactive Hisense computer-assisted system (CAS) for preoperative planning and intraoperative guidance during laparoscopic-assisted upper pancreatic lymph node dissection in distal gastrectomy for gastric cancer.

Methods: This study included 28 patients who underwent preoperative 3D reconstruction of the upper border of the pancreas using Hisense CAS (3D reconstruction group) for preoperative planning and intraoperative navigation. To determine its efficacy, the clinical data of these patients were compared with those of 28 patients who did not undergo 3D reconstruction (control group).

Results: Fifty-six cases of laparoscopic-assisted distal gastrectomy were performed. Three-dimensional reconstruction was successful in all the patients in the 3D reconstruction group, and real-time navigation was performed during the operation. The rate of correspondence between the 3D reconstruction images and intraoperative findings was 100%. The time taken for upper pancreatic lymph node dissection, number of upper pancreatic lymph node dissections, and number of unnecessary injuries during surgery were superior in the 3D reconstruction group than in the control group. The results of the remaining parameters were not statistically significant.

Conclusion: Preoperative planning with interactive Hisense CAS 3D reconstruction technology can improve surgeons' understanding of each patient's individual anatomy and can reveal anatomical variations, which is helpful for accurate preoperative planning and intraoperative navigation. This technique is helpful for the implementation of the precise dissection of lymph nodes at the upper edge of the pancreas and improves the quality and safety of the surgery.
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http://dx.doi.org/10.1016/j.asjsur.2020.12.034DOI Listing
May 2021

Gene expression pattern analysis using dual-color RT-MLPA and integrative genome-wide association studies of eQTL for tuberculosis suscepitibility.

Respir Res 2021 Jan 20;22(1):23. Epub 2021 Jan 20.

Department of Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China.

Background: When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood.

Methods: Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases.

Results: We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients.

Conclusion: We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.
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http://dx.doi.org/10.1186/s12931-020-01612-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816316PMC
January 2021

Near-Infrared-II Nanoparticles for Cancer Imaging of Immune Checkpoint Programmed Death-Ligand 1 and Photodynamic/Immune Therapy.

ACS Nano 2021 01 11;15(1):515-525. Epub 2021 Jan 11.

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.

Development of second near-infrared (NIR-II) nanoparticles (NPs) with high biocompatibility, low toxicity, and high singlet oxygen quantum yield (Φ) to prevent tumor recurrence is highly desirable in molecular imaging and photodynamic/immune combination therapy. Here, theranostic photosensitizer BODIPY (BDP)-I-N-anti-PD-L1 NPs were developed by encapsulating the photosensitizer BDP-I-N with amphipathic poly(styrene--chloromethylstyrene)--poly(ethylene glycol) nanocarriers through self-assembly functionalization with programmed cell death-ligand 1 (PD-L1) monoclonal antibody. These NPs exhibit highly intensive luminescence in the NIR-II window (1000-1700 nm) to real-time imaging of immune checkpoint PD-L1, high singlet oxygen quantum yield (Φ = 73%), and an eliminating effect of primary cancers. The NPs also allow for profiling PD-L1 expression as well as accumulating in MC38 tumor and enabling molecular imaging . Upon an 808 nm laser excitation, the targeted NPs produce an emission wavelength above 1200 nm to image a tumor to a normal tissue signal ratio (T/NT) at an approximate value of 14.1. Moreover, the MC38 tumors in mice are eliminated by combining photodynamic therapy and immunotherapy within 30 days, with no tumor recurrence within a period of 40 days. In addition, the tumors do not grow in the rechallenged mice within 7 days of inoculation. Such a strategy shows a durable immune memory effect against tumor rechallenging without toxic side effects to major organs.
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http://dx.doi.org/10.1021/acsnano.0c05317DOI Listing
January 2021

Biomass, lipid accumulation kinetics, and the transcriptome of heterotrophic oleaginous microalga Tetradesmus bernardii under different carbon and nitrogen sources.

Biotechnol Biofuels 2021 Jan 6;14(1). Epub 2021 Jan 6.

Department of Ecology, Research Center for Hydrobiology, Jinan University, Guangzhou, 510632, People's Republic of China.

Background: Heterotrophic cultivation of microalgae has been proposed as a viable alternative method for novel high-value biomolecules, enriched biomass, and biofuel production because of their allowance of high cell density levels, as well as simple production technology. Tetradesmus bernardii, a newly isolated high-yielding oleaginous microalga under photoautotrophic conditions, is able to grow heterotrophically, meaning that it can consume organic carbon sources in dark condition. We investigated the effect of different carbon/nitrogen (C/N) ratios on the growth and lipid accumulation of T. bernardii in heterotrophic batch culture under two nitrogen sources (NaNO and CO(NH)). In addition, we conducted time-resolved transcriptome analysis to reveal the metabolic mechanism of T. bernardii in heterotrophic culture.

Results: T. bernardii can accumulate high biomass concentrations in heterotrophic batch culture where the highest biomass of 46.09 g/L was achieved at 100 g/L glucose concentration. The rate of glucose to biomass exceeded 55% when the glucose concentration was less than 80 g/L, and the C/N ratio was 44 at urea treatment. The culture was beneficial to lipid accumulation at a C/N ratio between 110 and 130. NaNO used as a nitrogen source enhanced the lipid content more than urea, and the highest lipid content was 45% of dry weight. We performed RNA-seq to analyze the time-resolved transcriptome of T. bernardii. As the nitrogen was consumed in the medium, nitrogen metabolism-related genes were significantly up-regulated to speed up the N metabolic cycle. As chloroplasts were destroyed in the dark, the metabolism of cells was transferred from chloroplasts to cytoplasm. However, storage of carbohydrate in chloroplast remained active, mainly the synthesis of starch, and the precursor of starch synthesis in heterotrophic culture may largely come from the absorption of organic carbon source (glucose). With regard to lipid metabolism, the related genes of fatty acid synthesis in low nitrogen concentration increased gradually with the extension of cultivation time.

Conclusion: T. bernardii exhibited rapid growth and high lipid accumulation in heterotrophic culture. It may be a potential candidate for biomass and biofuel production. Transcriptome analysis showed that multilevel regulation ensured the conversion from carbon to the synthesis of carbohydrate and lipid.
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http://dx.doi.org/10.1186/s13068-020-01868-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789750PMC
January 2021