Publications by authors named "Yi Shi"

1,146 Publications

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Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics.

J Nanobiotechnology 2021 Nov 24;19(1):387. Epub 2021 Nov 24.

The Fourth Affiliated Hospital, Zhejiang University School of Medicine, 322000, Yiwu, Zhejiang, People's Republic of China.

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems.
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http://dx.doi.org/10.1186/s12951-021-01131-9DOI Listing
November 2021

Risk from Cooling Tower Systems in China.

Appl Environ Microbiol 2021 Nov 24:AEM0192121. Epub 2021 Nov 24.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichen West Road, Chaoyang District, Beijing 100101, China.

(LP) widely exists in natural and artificial water environments, which facilitates LP to infect people. LP infection causes Legionnaires' disease (LD), which is an important but relatively uncommon respiratory infection. Approximately 90% of LD is caused by serogroup 1 (Lp1). Meteorological conditions may affect the infectivity and virulence of Lp1, but the exact relationship between them is still unclear. In this study, we evaluated the virulence of Lp1 by screening of total 156 Lp1 strains isolated from cooling tower water in different region of China by detecting their abilities to activate NF-κB signaling pathway in vitro. In addition, we screened the distribution of some selected virulence genes in these strains. The virulence, virulence gene distribution and the meteorological factors were analyzed. We found that both the virulence and the distribution of virulence genes had a certain regional and meteorological correlation. Although loss of several virulence genes showed significant effects on the virulence of Lp1 strains, the distribution of virulence genes had very limited effects on the virulence of Lp1. LD is likely to be under-recognized in many countries. Due to the widespread existence of LP in natural and artificial water environments, and to the lack of cross-protection against different strains, LP is a potentially serious threat to human health. Therefore, effective monitoring of the virulence of LP in the water environment is very important to prevent and control the prevalence of LD. Understanding the virulence of LP can not only help us to predict the risk of possible outbreaks in advance, but can also enable more targeted clinical treatment. This study highlights the importance of understanding the epidemiology and ecology of LP isolated from public facilities in terms of public health and biology. Due to the potential for water sources to harbor and disseminate LP, and to the fact that geographical conditions influence the virulence of LP, timely and accurate LP virulence surveillance is urgently needed.
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http://dx.doi.org/10.1128/AEM.01921-21DOI Listing
November 2021

10 GHz regeneratively mode-locked thulium fiber laser with a stabilized repetition rate.

Opt Express 2021 Nov;29(23):37695-37702

GHz pulsed thulium-doped fiber laser with stabilized repetition rate can enable a wide range of applications. By employing regenerative mode-locking and cavity stabilization technique, we have for the first time demonstrated a 10 GHz polarization-maintaining thulium-doped fiber laser, which has a long-term repetition-rate stabilization and picosecond timing-jitter. In our experiment, a RF circuitry is designed to extract the 10 GHz longitudinal clock signal so that stable regenerative mode-locking is achieved. A piezo actuator-based phase-lock-loop is used to lock the regeneratively mode-locked pulses to a local reference synthesizer. The regeneratively mode-locked pulses with picosecond pulse width exhibit a high super-mode suppression ratio of 60 dB. In addition, the repetition rate of the laser shows good long-term stability with a variation of 8 Hz in 8 hours, corresponding to a cavity free spectral range fluctuation of less than 16 mHz. Meanwhile, the Allan deviation of the stabilized 10 GHz regeneratively mode-locked pulses is measured to be as low as 2 × 10 over 1000 s average time, which is only limited by the stability of the reference synthesizer. Such an ultra-stable 10 GHz pulsed thulium fiber laser may find potential application in 2 µm optical communication, material processing and spectroscopy.
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http://dx.doi.org/10.1364/OE.435537DOI Listing
November 2021

Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients.

Hum Immunol 2021 Nov 4. Epub 2021 Nov 4.

The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing 100039, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.
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http://dx.doi.org/10.1016/j.humimm.2021.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566346PMC
November 2021

The role of ceRNA-mediated diagnosis and therapy in hepatocellular carcinoma.

Hereditas 2021 Nov 10;158(1):44. Epub 2021 Nov 10.

College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, Hunan, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.
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http://dx.doi.org/10.1186/s41065-021-00208-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582193PMC
November 2021

Long-term cell culture and electrically monitoring of living cells based on a polyaniline hydrogel sensor.

J Mater Chem B 2021 Nov 10. Epub 2021 Nov 10.

State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Accurate, and long-term electrically monitoring of cell development plays an important role in cell study, which brings in challenges in terms of biocompatibility, processability, and sensing capability of electrochemical sensors. Based on biocompatible conductive polyaniline (PAni) hydrogels, we constructed a flexible sensor with flexible carbon cloth for electrical analysis of living cells. The carbon fiber substrate modified with conductive PAni hydrogels was selected as the electrode to promote the current collection of the sensor. The three dimensional nanostructured mesoporous matrix of PAni hydrogels is favorable for generation of catalytic Pt nanoparticles and cell growth. With these hierarchically nanostructured features, the hydrogel electrochemical sensor was endowed with high sensitivity and selectivity in the detection of HO (with a low detection limit of 1.6 μM in 0.01 M PBS and a wide linear range from 10 μM to 10 mM), and good biocompatibility for cell growth as long as 5 days. The accurate detection of HO released from cells enabled us to differentiate the physiological states of cells and imitate the different stimuli-responsive behavior, which can provide real-time information on cell biological events. With outstanding biocompatibility, operability and repeatability, this strategy can be expanded to the fields of other biosensor fabrication and cell-related biomarker monitoring, which exhibits a broad application potential in bioanalysis catering to new generation sensors.
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http://dx.doi.org/10.1039/d1tb01885jDOI Listing
November 2021

Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation.

Cell Biosci 2021 Nov 4;11(1):189. Epub 2021 Nov 4.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.

Background: Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2.

Methods: Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used.

Results: Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention.

Conclusions: We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771).
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http://dx.doi.org/10.1186/s13578-021-00701-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569968PMC
November 2021

Detection of BRCA1/2 Mutation and Analysis of Clinicopathological Characteristics in 141 Cases of Ovarian Cancer.

Comput Math Methods Med 2021 21;2021:4854282. Epub 2021 Oct 21.

Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China.

Breast cancer susceptibility genes 1 and 2 ( and ) are known biomarkers for hereditary ovarian cancer (OC). However, a comprehensive association study between mutation spectrum and clinicopathological characteristics in Chinese ovarian cancer patients has not been performed yet to our best knowledge. To fill in this gap, we collected sequencing data and clinical information of 141 OC patients from Fujian Cancer Hospital between April 2018 and March 2020. The clinical information includes the age of onset, FIGO staging, pathological types, serum 125 detection level, lymph node metastasis, distant metastasis, the expression of Ki67, and disease history of the patient and his/her family. We then studied their associations by software SciPy 1.0. As a result, we detected pathogenic and potentially pathogenic mutations in 27 out of 141 patients (19.15%). Among the 27 patients with mutations, the major type of mutation was frameshift, which was observed in 12 patients (44.4%). Most of the mutation sites were distributed on exons 10 and 11, accounting for 48.1% (13/27) and 22.2% (6/27), respectively. In terms of histological classification, high-grade serous adenocarcinoma accounted for 79.43% of the 141 samples. The mutation group was all high-grade serous adenocarcinoma, accounting for 24.1% (27/112) of this group. The incidence of pathogenic mutation in and was 15.7% (19/112) and 7.27% (8/112), respectively. Univariate analysis showed that there was no significant difference between patients with mutation and others in age-of-onset, FIGO stage, pathological types, serum CA125 level, lymph node metastasis, the expression of Ki67, and personal and family disease history. However, there are significant differences between patients with mutation and others in distant metastasis rate ( < 0.002). In addition, the mutation rate in 141 ovarian cancer patients was similar to those reported in other studies in China. Nearly one-quarter of high-grade serous carcinomas had BRCA1/2 mutations. In conclusion, our study indicated that patients with BRCA1/2 mutations were more likely to undergo distant metastasis, and BRCA1/2 mutation detection should be performed for patients with high-grade serous adenocarcinoma to guide the selection of clinical treatment options.
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http://dx.doi.org/10.1155/2021/4854282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554521PMC
October 2021

ARID1A deficiency weakens BRG1-RAD21 interaction that jeopardizes chromatin compactness and drives liver cancer cell metastasis.

Cell Death Dis 2021 10 23;12(11):990. Epub 2021 Oct 23.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

ARID1A, encoding a subunit of SWI/SNF chromatin remodeling complex, is widely recognized as a tumor suppressor gene in multiple tumor types including liver cancer. Previous studies have demonstrated that ARID1A deficiency can cause liver cancer metastasis, possibly due to the altered chromatin organization, however the underlying mechanisms remain poorly understood. To address the effect of Arid1a deficiency on chromatin organization, we generated chromatin interaction matrices, and exploited the conformation changes upon Arid1a depletion in hepatocytes. Our results demonstrated that Arid1a deficiency induced A/B compartment switching, topologically associated domain (TAD) remodeling, and decrease of chromatin loops. Further mechanism studies revealed that ATPase BRG1 of SWI/SNF complex could physically interact with RAD21, a structural subunit of chromatin architectural element cohesin; whereas ARID1A deficiency significantly diminished the coupled BRG1-RAD21. Interestingly, the tumor-associated genes within the switched compartments were differentially expressed depending upon Arid1a depletion or not. As a consequence of ARID1A deficiency-induced conformational alteration, the dysregulation of some genes such as PMP22 and GSC, promoted the invasion capacity of liver cancer cells. This study provides an insight into liver cancer tumorigenesis and progression related to ARID1A mutations.
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http://dx.doi.org/10.1038/s41419-021-04291-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542038PMC
October 2021

Heavy metal transporters: Functional mechanisms, regulation, and application in phytoremediation.

Sci Total Environ 2021 Oct 21:151099. Epub 2021 Oct 21.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Heavy metal pollution in soil is a global problem with serious impacts on human health and ecological security. Phytoextraction in phytoremediation, in which plants uptake and transport heavy metals (HMs) to the tissues of aerial parts, is the most environmentally friendly method to reduce the total amount of HMs in soil and has wide application prospects. However, the molecular mechanism of phytoextraction is still under investigation. The uptake, translocation, and retention of HMs in plants are mainly mediated by a variety of transporter proteins. A better understanding of the accumulation strategy of HMs via transporters in plants is a prerequisite for the improvement of phytoextraction. In this review, the biochemical structure and functions of HM transporter families in plants are systematically summarized, with emphasis on their roles in phytoremediation. The accumulation mechanism and regulatory pathways related to hormones, regulators, and reactive oxygen species (ROS) of HMs concerning these transporters are described in detail. Scientific efforts and practices for phytoremediation carried out in recent years suggest that creation of hyperaccumulators by transgenic or gene editing techniques targeted to these transporters and their regulators is the ultimate powerful path for the phytoremediation of HM contaminated soils.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151099DOI Listing
October 2021

Comparative Secretomics Analysis Reveals the Major Components of 16 and RUT-C30.

Microorganisms 2021 Sep 27;9(10). Epub 2021 Sep 27.

College of Life Science, Jiangxi Normal University, Nanchang 330022, China.

In this study, the major secretome components of 16 and RUT-C30 under wheat bran (WB) and rice straw (RS) solid-state fermentation were systematically analyzed. The activities of the major components, e.g., cellulase, hemicellulase, and amylase, were consistent with their abundance in the secretomes. 16 secreted more abundant glycoside hydrolases than RUT-C30. The main up-regulated proteins from the induction of WB, compared with that from RS, were amylase, pectinase, and protease, whereas the main down-regulated enzymes were cellulase, hemicellulase, swollenin, and lytic polysaccharide monooxygenase (LPMO). Specifically, WB induced more β-1,4-glucosidases, namely, S8B0F3 (UniProt ID), and A0A024RWA5 than RS, but RS induced more β-1,4-exoglucanases and β-1,4-endoglucanases, namely, A0A024RXP8, A024SH76, S7B6D6, S7ZP52, A024SH20, A024S2H5, S8BGM3, S7ZX22, and S8AIJ2. The 16 xylanases S8AH74 and S7ZA57 were the major components responsible for degrading soluble xylan, and S8BDN2 probably acted on solid-state hemicellulose instead of soluble xylan. The main hemicellulase component of RUT-C30 in RS was the xyloglucanase A0A024S9Z6 with an abundance of 16%, but RUT-C30 lacked the hemicellulase mannanase and had a small amount of the hemicellulase xylanase. 16 produced more amylase than RUT-C30, and the results suggest amylase S7Z6T2 may degrade soluble starch. The percentage of the glucoamylase S8B6D7 did not significantly change, and reached an average abundance of 5.5%. The major auxiliary degradation enzymes of 16 were LPMOs S7Z716 and S7ZPW1, whereas those of RUT-C30 were swollenin and LPMOs A0A024SM10, A0A024SFJ2, and A0A024RZP7.
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http://dx.doi.org/10.3390/microorganisms9102042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538001PMC
September 2021

Astaxanthin Provides Antioxidant Protection in LPS-Induced Dendritic Cells for Inflammatory Control.

Mar Drugs 2021 Sep 23;19(10). Epub 2021 Sep 23.

College of Food Science and Engineering, Yangzhou University, Yangzhou 225009, China.

Astaxanthin, originating from marine organisms, is a natural bioactive compound with powerful antioxidant activity. Here, we evaluated the antioxidant ability of astaxanthin on dendritic cells (DCs), a key target of immune regulation, for inflammatory control in a sepsis model. Our results showed that astaxanthin suppressed nitric oxide (NO) production, reactive oxygen species (ROS) production, and lipid peroxidation activities in LPS-induced DCs and LPS-challenged mice. Moreover, the reduced glutathione (GSH) levels and the GSH/GSSG ratio were increased, suggesting that astaxanthin elevated the level of cellular reductive status. Meanwhile, the activities of antioxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were significantly upregulated. Astaxanthin also inhibited the LPS-induced secretions of IL-1β, IL-17, and TGF-β cytokines. Finally, we found that the expressions of heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly upregulated by astaxanthin in LPS-induced DCs, suggesting that the HO-1/Nrf2 pathway plays a significant role in the suppression of oxidative stress. These results suggested that astaxanthin possesses strong antioxidant characteristics in DC-related inflammatory responses, which is expected to have potential as a method of sepsis treatment.
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http://dx.doi.org/10.3390/md19100534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540215PMC
September 2021

LongTerm Outcomes of Three-Port Laparoscopic Right Hemicolectomy Five-Port Laparoscopic Right Hemicolectomy: A Retrospective Study.

Front Oncol 2021 30;11:762716. Epub 2021 Sep 30.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: The aim of this study is to compare the long-term outcomes of three-port laparoscopic right hemicolectomy (TPLRC) and five-port laparoscopic right hemicolectomy (FPLRC) with retrospective analysis.

Methods: A total of 182 patients who accepted laparoscopic right hemicolectomy with either three ports (86 patients) or five ports (96 patients) from January 2012 to June 2017 were non-randomly selected and analyzed retrospectively.

Results: More lymph nodes were harvested in the TPLRC group than in the FPLRC group [17.5 (7), 14 (8) ml, < 0.001]. There was less blood loss in the TPLRC group [50 (80) . 100 (125) ml, = 0.015]. There were no significant differences in the other short-term or oncological outcomes between the two groups. The overall survival and disease-free survival were equivalent.

Conclusions: TPLRC is recommendable as it guarantees short- and long-term equivalent outcomes compared with FPLRC.
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http://dx.doi.org/10.3389/fonc.2021.762716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514867PMC
September 2021

Exploring the Influence Factors of Early Hydration of Ultrafine Cement.

Materials (Basel) 2021 Sep 29;14(19). Epub 2021 Sep 29.

Metals & Chemistry Research Institute, China Academy of Railway Sciences Corporation Limited, Beijing 100081, China.

This work intends to contribute to the understanding of the influence factors of early hydration of ultrafine cement by focusing on the different fineness, different kinds of hardening accelerators, and different curing temperatures. Isothermal calorimetry, thermogravimetry, and X-ray diffraction (XRD) were performed to compare the hydration and chemical evolution of pastes containing accelerators with different fineness and curing temperatures; meanwhile, mechanical properties and water absorption were tested. The results showed that the cement fineness had a significant effect on the early hydration process; the smaller the cement particle size, the higher the early compressive strength. The 24 h compressive strength of ultrafine cement with a particle diameter of 6.8μm could reach 55.94 MPa, which was 118% higher than the reference cement. Water absorption test results indicated that adding 1% Ca(HCOO) to ultrafine cement can effectively reduce the water absorption, and it was only 1.93% at 28 d, which was 46% lower than the reference cement. An increase in curing temperature accelerated the activation of ultrafine cement in terms of the strength development rate, and the content of Ca(OH) in the ultrafine cement paste could reach 13.09% after being mixed with water for 24 h, which was 22% higher than that of the reference cement.
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http://dx.doi.org/10.3390/ma14195677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510312PMC
September 2021

MicroRNA-324-3p Plays A Protective Role Against Coxsackievirus B3-Induced Viral Myocarditis.

Virol Sin 2021 Oct 11. Epub 2021 Oct 11.

School of Medicine College, Jiangsu University, Zhenjiang, 212013, China.

Viral myocarditis (VM) is an inflammatory disease of the myocardium associated with heart failure, which is caused by common viral infections. A majority of the infections are initiated by coxsackievirus B3 (CVB3). MicroRNAs (miRNAs) have a major role in various biological processes, including gene expression, cell growth, proliferation, and apoptosis, as well as viral infection and antiviral immune responses. Although, miRNAs have been found to regulate viral infections, their role in CVB3 infection remains poorly understood. In the previous study, miRNA microarray results showed that miR-324-3p expression levels were significantly increased when cells and mice were infected with CVB3. It was also found that miR-324-3p downregulated TRIM27 and decreased CVB3 replication in vitro and in vivo. In vitro, analysis of downstream signaling of TRIM27 revealed that, miR-324-3p inhibited CVB3 infection, and reduced cytopathic effect and viral plaque formation by reducing the expression of TRIM27. In vivo, miR-324-3p decreased the expression of TRIM27, reduced cardiac viral replication and load, thereby strongly attenuating cardiac injury and inflammation. Taken together, this study suggests that miR-324-3p targets TRIM27 to inhibit CVB3 replication and viral load, thereby reducing the cardiac injury associated with VM.
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http://dx.doi.org/10.1007/s12250-021-00441-4DOI Listing
October 2021

The Treatment of Cholecystitis and Cholelithiasis by Tibetan Medicine.

Evid Based Complement Alternat Med 2021 30;2021:9502609. Epub 2021 Sep 30.

Qinghai Jiumei Tibetan Medicine Co., Ltd., Xining 810000, China.

Cholecystitis and cholelithiasis is one of the factors threatening human health. It is very important to find drugs for the treatment of cholecystitis and cholelithiasis. Tibetan medicine is one of the traditional medical systems in China. It has rich experience in treating various diseases. This paper summarizes the treatment of cholecystitis and cholelithiasis through literature review of Tibetan medicine monographs, drug standards, Tibetan medicine, and prescriptions. In the Tibetan medicine system, 170 kinds of Tibetan medicine and 38 kinds of Tibetan prescriptions were found to treat cholecystitis and cholelithiasis. Among them, there are 35 modern researches related to the treatment of cholecystitis and cholelithiasis. Their names, families, medicinal parts, chemical constituents, and pharmacological activities are introduced in detail. These Tibetan medicines and prescriptions may be a precious gift of ancient Tibetan medicine to the world, and may also become potential drug candidates for the treatment of cholecystitis and cholelithiasis. Modern phytochemistry, pharmacology, metabonomics, and/or clinical trials can be used to confirm its medicinal value in the treatment of cholecystitis and cholelithiasis, identify active compounds, clarify its potential mechanism of action, and clarify its toxicity and side effects. This article provides a new idea and source for the treatment of cholecystitis and cholelithiasis.
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http://dx.doi.org/10.1155/2021/9502609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497101PMC
September 2021

Genome-wide analysis of DNA methylation in 106 schizophrenia family trios in Han Chinese.

EBioMedicine 2021 Oct 7;72:103609. Epub 2021 Oct 7.

Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, PR China. Electronic address:

Background: Schizophrenia (SCZ) is a severe psychiatric disorder that affects approximately 0.75% of the global population. Both genetic and environmental factors contribute to development of SCZ. SCZ tends to run in family while both genetic and environmental factor contribute to its etiology. Much evidence suggested that alterations in DNA methylations occurred in SCZ patients.

Methods: To investigate potential inheritable pattern of DNA methylation in SCZ family, we performed a genome-wide analysis of DNA methylation of peripheral blood samples from 106 Chinese SCZ family trios. Genome-wide DNA methylations were quantified by Agilent 1 × 244 k Human Methylation Microarray.

Findings: In this study, we proposed a loci inheritance frequency model that allows characterization of differential methylated regions as SCZ biomarkers. Based on this model, 112 hypermethylated and 125 hypomethylated regions were identified. Additionally, 121 hypermethylated and 139 hypomethylated genes were annotated. The results of functional enrichment analysis indicated that multiple differentially methylated genes (DMGs) involved in Notch/HH/Wnt signaling, MAPK signaling, GPCR signaling, immune response signaling. Notably, a number of hypomethylated genes were significantly enriched in cerebral cortex and functionally enriched in nervous system development.

Interpretation: Our findings not only validated previously discovered risk genes of SCZ but also identified novel candidate DMGs in SCZ. These results may further the understanding of altered DNA methylations in SCZ.

Funding: None.
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http://dx.doi.org/10.1016/j.ebiom.2021.103609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511801PMC
October 2021

Clinical features of cryptococcosis in patients with different immune statuses: a multicenter study in Jiangsu Province-China.

BMC Infect Dis 2021 Oct 8;21(1):1043. Epub 2021 Oct 8.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China.

Background: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat.

Methods: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression).

Results: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015).

Conclusions: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.
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http://dx.doi.org/10.1186/s12879-021-06752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499499PMC
October 2021

Tracing the origins of SARS-CoV-2: lessons learned from the past.

Cell Res 2021 11;31(11):1139-1141

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

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http://dx.doi.org/10.1038/s41422-021-00575-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480455PMC
November 2021

Elevated Stratifin promotes cisplatin-based chemotherapy failure and poor prognosis in non-small cell lung cancer.

Mol Ther Oncolytics 2021 Sep 21;22:326-335. Epub 2021 Jul 21.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Drug resistance is a key factor in the treatment failure of clinical non-small cell lung cancer (NSCLC) patients after adjuvant chemotherapy. Here, our results provide the first evidence that eukaryotic translation initiation factor 2b subunit delta (EIF2B4)-Stratifin (SFN) fusion and increased SFN expression are associated with chemotherapy tolerance and activation of the phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) signaling pathway in NSCLC patients, suggesting that SFN might have potential prognostic value as a tumor biomarker for the prognosis of patients with NSCLC.
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http://dx.doi.org/10.1016/j.omto.2021.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426184PMC
September 2021

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition.

J Transl Med 2021 09 22;19(1):400. Epub 2021 Sep 22.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301, Yanchang Middle Road, Jing'an District, Shanghai, 200072, China.

Background: Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness.

Methods: Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells.

Results: LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo.

Conclusion: Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.
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http://dx.doi.org/10.1186/s12967-021-03052-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456629PMC
September 2021

A resource of high-quality and versatile nanobodies for drug delivery.

iScience 2021 Sep 21;24(9):103014. Epub 2021 Aug 21.

Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Therapeutic and diagnostic efficacies of small biomolecules and chemical compounds are hampered by suboptimal pharmacokinetics. Here, we developed a repertoire of robust and high-affinity antihuman serum albumin nanobodies (Nb) that can be readily fused to small biologics for half-life extension. We characterized the thermostability, binding kinetics, and cross-species reactivity of Nbs, mapped their epitopes, and structurally resolved a tetrameric HSA-Nb complex. We parallelly determined the half-lives of a cohort of selected Nbs in an HSA mouse model by quantitative proteomics. Compared to short-lived control nanobodies, the half-lives of Nbs were drastically prolonged by 771-fold. Nbs have distinct and diverse pharmacokinetics, positively correlating with their albumin binding affinities at the endosomal pH. We then generated stable and highly bioactive Nb-cytokine fusion constructs "Duraleukin" and demonstrated Duraleukin's high preclinical efficacy for cancer treatment in a melanoma model. This high-quality and versatile Nb toolkit will help tailor drug half-life to specific medical needs.
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http://dx.doi.org/10.1016/j.isci.2021.103014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426283PMC
September 2021

MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211041191

Shanghai Tenth People's Hospital, 278245Tongji University School of Medicine, Shanghai, China.

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.
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http://dx.doi.org/10.1177/15330338211041191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445543PMC
September 2021

Unusual cause of gastrointestinal bleeding in an 84-year-old woman: a miraculous survival from an aortoduodenal fistula repair.

BMJ Case Rep 2021 Sep 13;14(9). Epub 2021 Sep 13.

Vascular Surgery, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.

An 84-year-old woman presented acutely with dizziness, fatigue and a total of 800 mL of fresh per rectum (PR) bleeding. The significant history of abdominal aortic aneurysm repair 5 years ago included multiple episodes of endovascular leak around the stent associated with abscess of left psoas major, left abdominal wall abscess with sinus formation, appendicitis with abscess formation, and acute pancreatic and chronic cholecystitis with multiple gallstones in the 7 months prior to this presentation. During the preceding 7 months, the patient was stabilised with an intravenous proton pump inhibitor, blood transfusions and Intensive Care Unit (ICU) management for the assumed diagnosis of stress ulcers over multiple hospital admissions. Imaging with CT scan of the abdomen made the more accurate diagnosis of acute gastrointestinal haemorrhage caused by a fistula between the distal duodenum and aorta, which was later surgically confirmed. Removal of infected stents and axillobifemoral bypass were performed with a successful recovery.
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http://dx.doi.org/10.1136/bcr-2021-244318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438823PMC
September 2021

Three-dimensional monolithic micro-LED display driven by atomically thin transistor matrix.

Nat Nanotechnol 2021 Nov 9;16(11):1231-1236. Epub 2021 Sep 9.

National Laboratory of Solid State Microstructures, School of Electronic Science and Engineering and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.

Two-dimensional materials are promising candidates for future electronics due to unmatched device performance at atomic limit and low-temperature heterogeneous integration. To adopt these emerging materials in computing and optoelectronic systems, back end of line (BEOL) integration with mainstream technologies is needed. Here, we show the integration of large-area MoS thin-film transistors (TFTs) with nitride micro light-emitting diodes (LEDs) through a BEOL process and demonstrate high-resolution displays. The MoS transistors exhibit median mobility of 54 cm Vs , 210 μA μm drive current and excellent uniformity. The TFTs can drive micrometre-sized LEDs to 7.1 × 10 cd m luminance under low voltage. Comprehensive analysis on driving capability, response time, power consumption and modulation scheme indicates that MoS TFTs are suitable for a range of display applications up to the high resolution and brightness limit. We further demonstrate prototypical 32 × 32 active-matrix displays at 1,270 pixels-per-inch resolution. Moreover, our process is fully monolithic, low-temperature, scalable and compatible with microelectronic processing.
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http://dx.doi.org/10.1038/s41565-021-00966-5DOI Listing
November 2021

Immobilization of Phospholipase A1 Using a Protein-Inorganic Hybrid System.

Polymers (Basel) 2021 Aug 26;13(17). Epub 2021 Aug 26.

National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.

In this study, four kinds of phospholipase A1-metal (Al/Co/Cu/Mn) hybrid nanostructures were prepared for enhancing the stability of the free PLA1. The formed hybrid complexes were characterized by scanning electron microscope (SEM), Fourier infrared spectroscopy (FTIR), and -ray diffraction (XRD). The stability and substrate specificity of immobilized enzymes were subsequently determined. After immobilization, the temperature tolerance of PLA1-metal hybrid nanostructures was enhanced. The relative activity of PLA1-Al/Co/Cu hybrid nanostructures remained above 60% at 50 °C, while that of free enzyme was below 5%. The thermal transition temperature measured by differential scanning calorimetry (DSC) was found to increase from 65.59 °C (free enzyme) to 173.14 °C, 123.67 °C, 96.31 °C, and 114.79 °C, referring to PLA1-Cu/Co/Al/Mn hybrid nanostructures, respectively. Additionally, after a storage for fourteen days at 4 °C, the immobilized enzymes could exhibit approximately 60% of the initial activity, while the free PLA1 was inactivated after four days of storage. In brief, using Co, Cu, Al, and Mn as the hybridization materials for immobilization could improve the catalytic properties and stability of the free PLA1, suggesting a promising method for a wider application of PLA1 in many fields such as food, cosmetics, and the pharmaceutical industry.
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http://dx.doi.org/10.3390/polym13172865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433775PMC
August 2021

Correction to: Surface-imprinted β-cyclodextrin-functionalized carbon nitride nanosheets for fluorometric determination of sterigmatocystin.

Mikrochim Acta 2021 Sep 8;188(10):332. Epub 2021 Sep 8.

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 211198, China.

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http://dx.doi.org/10.1007/s00604-021-04961-4DOI Listing
September 2021

Epitaxial growth of wafer-scale molybdenum disulfide semiconductor single crystals on sapphire.

Nat Nanotechnol 2021 Nov 2;16(11):1201-1207. Epub 2021 Sep 2.

National Laboratory of Solid State Microstructures, School of Electronic Science and Engineering and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, China.

Two-dimensional (2D) semiconductors, in particular transition metal dichalcogenides (TMDCs), have attracted great interest in extending Moore's law beyond silicon. However, despite extensive efforts, the growth of wafer-scale TMDC single crystals on scalable and industry-compatible substrates has not been well demonstrated. Here we demonstrate the epitaxial growth of 2 inch (~50 mm) monolayer molybdenum disulfide (MoS) single crystals on a C-plane sapphire. We designed the miscut orientation towards the A axis (C/A) of sapphire, which is perpendicular to the standard substrates. Although the change of miscut orientation does not affect the epitaxial relationship, the resulting step edges break the degeneracy of nucleation energy for the antiparallel MoS domains and lead to more than a 99% unidirectional alignment. A set of microscopies, spectroscopies and electrical measurements consistently showed that the MoS is single crystalline and has an excellent wafer-scale uniformity. We fabricated field-effect transistors and obtained a mobility of 102.6 cm V s and a saturation current of 450 μA μm, which are among the highest for monolayer MoS. A statistical analysis of 160 field-effect transistors over a centimetre scale showed a >94% device yield and a 15% variation in mobility. We further demonstrated the single-crystalline MoSe on C/A sapphire. Our method offers a general and scalable route to produce TMDC single crystals towards future electronics.
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http://dx.doi.org/10.1038/s41565-021-00963-8DOI Listing
November 2021

Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment.

Evid Based Complement Alternat Med 2021 21;2021:9987097. Epub 2021 Aug 21.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China.

Traditional Chinese medicine (TCM) has good clinical application prospects in diabetes treatment. In addition, TCM is less toxic and/or has fewer side effects and provides various therapeutic effects. Berberine (BBR) is isolated as the main component in many TCM kinds (e.g., and ). Furthermore, BBR can reduce blood sugar and blood fat, alleviate inflammation, and improve the state of patients. Based on the recent study results of BBR in diabetes treatment, the BBR pharmacokinetics and mechanism on diabetes are mainly studied, and the specific molecular mechanism of related experimental BBR is systematically summarized and analyzed. Clinical studies have proved that BBR has a good therapeutic effect on diabetes, suggesting that BBR may be a promising drug candidate for diabetes. More detailed BBR mechanisms and pathways of BBR need to be studied further in depth, which will help understand the BBR pharmacology in diabetes treatment.
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http://dx.doi.org/10.1155/2021/9987097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405293PMC
August 2021

Precision Wormlike Nanoadjuvant Governs Potency of Vaccination.

Nano Lett 2021 09 30;21(17):7236-7243. Epub 2021 Aug 30.

School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China.

It remains unclear how the precise length of one-dimensional nanovehicles influences the characters of vaccination. Here, a unimolecular nanovehicle with tailored size and aspect ratio (AR) is applied to deliver CpG oligodeoxynucleotide, a Toll-like receptor (TLR) 9 agonist, as an adjuvant of recombinant hepatitis B virus surface antigen (rHBsAg), for treating chronic hepatitis B (CHB). Cationic nanovehicles with fixed width (ca. 45 nm) but varied length (46 nm-180 nm), AR from 1 to 4, are prepared through controlled polymerization and are loaded with CpG by electrostatic interaction. We reveal that the nanoadjuvant with AR = 2 shows the highest retention in proximal lymph nodes. Importantly, it is more easily internalized into antigen-presenting cells and accumulates in the late endosome, where TLR9 is located. Such a nanoadjuvant exhibits the strongest immune response with rHBsAg to clear the hepatitis B virus in the CHB mouse model, showing that the AR of nanovehicles governs the efficiency of vaccination.
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http://dx.doi.org/10.1021/acs.nanolett.1c02274DOI Listing
September 2021
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