Publications by authors named "Jin Sun"

872 Publications

Small-Molecule Prodrug Nanoassemblies: An Emerging Nanoplatform for Anticancer Drug Delivery.

Small 2021 Aug 3:e2101460. Epub 2021 Aug 3.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.

The antitumor efficiency and clinical translation of traditional nanomedicines is mainly restricted by low drug loading, complex preparation technology, and potential toxicity caused by the overused carrier materials. In recent decades, small-molecule prodrug nanoassemblies (SMP-NAs), which are formed by the self-assembly of prodrugs themselves, have been widely investigated with distinct advantages of ultrahigh drug-loading and negligible excipients-trigged adverse reaction. Benefited from the simple preparation process, SMP-NAs are widely used for chemotherapy, phototherapy, immunotherapy, and tumor diagnosis. In addition, combination therapy based on the accurate co-delivery behavior of SMP-NAs can effectively address the challenges of tumor heterogeneity and multidrug resistance. Recent trends in SMP-NAs are outlined, and the corresponding self-assembly mechanisms are discussed in detail. Besides, the smart stimuli-responsive SMP-NAs and the combination therapy based on SMP-NAs are summarized, with special emphasis on the structure-function relationships. Finally, the outlooks and potential challenges of SMP-NAs in cancer therapy are highlighted.
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http://dx.doi.org/10.1002/smll.202101460DOI Listing
August 2021

Probing the fluorination effect on the self-assembly characteristics, fate and antitumor efficacy of paclitaxel prodrug nanoassemblies.

Theranostics 2021 6;11(16):7896-7910. Epub 2021 Jul 6.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Small-molecule prodrug nanoassembly is emerging as an efficient platform for chemotherapy. The self-assembly stability plays a vital role on the drug delivery efficiency of prodrug nanoassembly. It is reported that fluoroalkylation could improve the self-assembly stability of amphiphilic polymers by utilizing the unique fluorination effect. But the application of fluoroalkylation on small-molecule prodrug nanoassembly has never been reported. Here, fluoro-modified prodrug was developed by conjugating paclitaxel with perfluorooctanol (F-SS-PTX), and the paclitaxel-octanol prodrug (C-SS-PTX) was used as control. The fluoro-mediated self-assembly mechanisms were illustrated using molecular dynamics simulation. In addition, the impacts of fluoroalkylation on the pharmacy characters, fate and antitumor effect of small-molecule prodrug nanoassembly were investigated in details. Fluoroalkylation significantly improved the self-assembly stability of F-SS-PTX NPs both and , which could be attributed to the fluoro-mediated hydrophobic force and halogen bonds. The AUC and tumor accumulation of F-SS-PTX NPs was 6-fold and 2-fold higher than that of C-SS-PTX NPs, respectively. As a result, F-SS-PTX NPs exhibited much better antitumor effect than C-SS-PTX NPs and Abraxane. Fluoroalkylation could improve the self-assembly stability, fate, and antitumor efficacy of small-molecule prodrug nanoassemblies, which could be an effective strategy for the rational design of advanced nanomedicines.
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http://dx.doi.org/10.7150/thno.61337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315070PMC
July 2021

Nonlinear features of Fano resonance: a QM/EM study.

Phys Chem Chem Phys 2021 Aug;23(30):15994-16004

State Key Laboratory of Physical Chemistry of Solid Surfaces, Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, People's Republic of China.

The nonlinear Fano effects on the absorption of hybrid systems composed of a silver nanosphere and an indoline dye molecule have been systematically investigated by the hybrid approach, which combines the quantum mechanics method (QM) with the computational electromagnetic method (EM). The absorption spectra of the dye molecule in the proximity of an Ag nanoparticle have been calculated by changing the incident field intensity, the phenomenological dephasing of molecular excitation, and the enhancement ratio of the near field. The contribution of molecular nonlinear response properties and the quantum interferences of the incident and scattered fields and of resonant plasmon-molecular excitations to the spectra has been identified. It is in no doubt that Fano resonance due to the plasmon-molecular interaction can appear in both the weak and strong field regimes; however, the Fano effect is more pronounced in the strong field regime where quantum interference leads to a nonlinear Fano effect controlled by a complex field-dependent Fano factor. When the incident field is strong enough, the resonance antisymmetry structure is spectrally resolved, and it changes with the change of the field intensity. As the field intensity varies from weak to strong, the Fano lineshape's asymmetry increases with increasing intensity in the beginning, and then decreases with a further increase of the field intensity attributed to the increase of the detuning energy induced by the integrated energy shift upon field dressing during the excitation. Decreasing the enhancement ratio of the near field or the dephasing of molecular excitation can also control the spectral lineshape transformation from an asymmetric profile to a symmetric Lorentzian lineshape. These findings are consistent with previous experimental and theoretical observations arisen by quantum interferences and are expected to stimulate further work toward exploring the plasmon-molecular interplay and the applications of Fano resonance in optical switching and sensing.
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http://dx.doi.org/10.1039/d1cp02459kDOI Listing
August 2021

Comparative efficacy of osteochondral autologous transplantation and microfracture in the knee: an updated meta-analysis of randomized controlled trials.

Arch Orthop Trauma Surg 2021 Jul 25. Epub 2021 Jul 25.

Department of Arthroscopy and Sports Medicine, China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, 100102, China.

Introduction: More than 19% of patients undergoing knee arthroscopies suffers from articular cartilage defects. The chondral or osteochondral lesion has negative impacts on the knee joints function and the life quality of patients. However, the treatment remains challenging as hyaline cartilage is not renewable. The purpose of this study was to systematically analyze the data of randomized controlled trials for comparing the postoperative outcomes between osteochondral autologous transplantation (OAT) and microfracture (MF) procedure. We hypothesized that the outcomes were better in OAT than MF procedure.

Materials And Methods: A systematic literature search of the EMBASE, Pubmed, and Cochrane Library databases was conducted based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The outcome measures include: the rate of excellent or good results, the rate of return to sports, the failure rate, osteoarthritis rate, International Cartilage Repair Society (ICRS) score, Lysholm Knee Score, and Tegner scale. The statistical analysis was completed using Review Manager (RevMan, version 5.3) software.

Results: The systematic search identified 7 studies with a total of 346 patients. The pooled result showed significant differences between the two groups in the rate of return to sports and failure. The following outcome scores showed significant improvement (pre- vs postoperatively): Lysholm score (p = 0.02), Tegner scale (p < 0.00001), and ICRS score (p < 0.00001). The differences were not significant in the excellent or good results and the rate of osteoarthritis.

Conclusion: The patients in OAT group may return to play quicker, even return to pre-injury level of activity compared to the MF group. OAT is better than MF procedure in accordance with Lysholm score, Tegner score, ICRS score, and the rate of failure. However, few studies have reported long-term outcomes and there has no uniform criteria for safe return to sports. Further research is needed.

Level Of Evidence: Level II, meta-analysis of randomized controlled trials.
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http://dx.doi.org/10.1007/s00402-021-04075-9DOI Listing
July 2021

The high normal ankle brachial index is associated with left ventricular hypertrophy in hypertension patients among the Han Chinese.

J Clin Hypertens (Greenwich) 2021 Jul 23. Epub 2021 Jul 23.

Department of Geriatrics, The second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9-1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40-75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m for men and 46.7 g/m for women. Our study suggested that the ABI was higher in patients with LVH than in those without (1.13±0.11, 1.11±0.11, p < 0.001). The prevalence of LVH in patients with the lowest (0.9 < ABI≤1.03), second (1.04≤ABI≤1.11), the third (1.12≤ABI≤1.20), and the highest quartile (1.21≤ABI < 1.40) of ABI was 37.2%, 38.2%, 45.5%, 45.7%, respectively. Logistic regression analysis suggested that the highest and third quartile of ABI were significantly associated with increased LVH risk (multivariate-adjusted OR of highest group:1.83; third group:1.61). The association of ABI at second quartile with LVH was nonsignificant. Similar results were observed in less than 60 years and without coronary heart disease or diabetes group. Our observations in Chinese patients with hypertension indicated high ABI may be an important risk factor for LVH in hypertension patients among Han Chinese, even in the normal range.
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http://dx.doi.org/10.1111/jch.14328DOI Listing
July 2021

escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5.

J Med Microbiol 2021 Jul;70(7)

Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, PR China.

is an intracellular bacterial pathogen that utilizes a type III secretion apparatus to inject effector proteins into host cells. The T3SS effector IpaH4.5 is important for the virulence of . This study aimed to elucidate the molecular mechanism and host target of the IpaH4.5 as well as its roles in infection. The GAP assay was used to identify substrate Rab GTPases of IpaH4.5. A coimmunoprecipitation assay was applied to identify the interaction of Rab GTPases with IpaH4.5. A confocal microscopy analysis was used to assess the effects of IpaH4.5 on mannose 6-phosphate receptor (MPR) trafficking. To identify the effects of IpaH4.5 GAP activity on the activity of lysosomal cathepsin B, the Magic Red-RR assay was used. Finally, the intracellular persistence assay was used to identify IpaH4.5 GAP activity in intracellular growth. We found that the effector IpaH4.5 disrupts MPR trafficking and lysosomal function, thereby counteracting host lysosomal degradation. IpaH4.5 harbours TBC-like dual-finger motifs and exhibits potent RabGAP activities towards Rab31. IpaH4.5 disrupts the transport of the cation-dependent mannose 6-phosphate receptor (CD-MPR) from the Golgi to the endosome by targeting Rab31, thereby attenuating lysosomal function. As a result, the intracellular persistence of requires IpaH4.5 TBC-like GAP activity to mediate bacterial escape from host lysosome-mediated elimination. We identified an unknown function of IpaH4.5 and its potential role in infection.
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http://dx.doi.org/10.1099/jmm.0.001382DOI Listing
July 2021

Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies.

Asian J Pharm Sci 2021 May 25;16(3):337-349. Epub 2021 Feb 25.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Homodimeric prodrug-based self-assembled nanoparticles, with carrier-free structure and ultrahigh drug loading, is drawing more and more attentions. Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage. The influence of the linkages on the self-assembly, fate and antitumor activity of homodimeric prodrugs is the focus of research. Herein, three docetaxel (DTX) homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages. Interestingly, compared with the other two linkages, the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs, thus improving the stability, circulation time and tumor targeting of prodrug nanoassemblies. Besides, the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells. Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells, their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells, which finally "turned the table". Our study illustrates the crucial role of linkages in homodimeric prodrugs, and gives valuable proposal for the development of advanced nano-DDS for cancer treatment.
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http://dx.doi.org/10.1016/j.ajps.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261084PMC
May 2021

Use of the alkaline comet assay for monitoring genotoxic effects of arsenic in human populations.

Mutat Res Genet Toxicol Environ Mutagen 2021 07 1;867:503368. Epub 2021 Jun 1.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023, Nanjing, China. Electronic address:

The alkaline comet assay has been widely used to determine genotoxicity in human populations exposed to arsenic. The sample sizes of earlier studies were usually small, and inconsistent results were found. Meta-analyses can merge the results of multiple studies of the same type and increase the credibility of the conclusion by increasing the sample size. Thus, to investigate the monitoring effect of alkaline comet assay on genotoxicity for arsenic exposed population, meta-analyses were performed. Thirteen studies were found to meet the inclusion criteria and were included in this study; of them, twelve articles were of medium quality (15-20 points), only one study was of high quality (21-27 points). Meta-analyses showed that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by that in the reference group) were 2.81(95 % confidence interval (CI) 1.93-4.10); 2.37(95 % CI, 1.73-3.26), and 1.69(95 %CI, 1.29-2.20) for comet tail length, % tail DNA, and tail moment, respectively. This shows that the level of DNA damage in arsenic exposed population is significantly higher than that in control populations. A meta-analysis of the correlation coefficients showed that the overall estimate was 0.52 (95 %CI, 0.48∼0.56, P<0.05) with all correlation coefficients included, but it changed to 0.24 (95 %CI, 0.17∼0.28, P<0.05) when two abnormal correlation coefficients were excluded, suggesting there was a positive correlation between arsenic load in vivo and DNA damage, but the overall estimate value of coefficients was unstable. Therefore, we conclude that the alkaline comet assay can be used as an effective genotoxic biomonitoring tool for arsenic-exposed populations. However, more and higher-quality studies are still needed to verify its actual application value.
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http://dx.doi.org/10.1016/j.mrgentox.2021.503368DOI Listing
July 2021

Early child development in low- and middle-income countries: Is it what mothers have or what they do that makes a difference to child outcomes?

Adv Child Dev Behav 2021 26;61:255-277. Epub 2021 Jun 26.

OISE, University of Toronto, Toronto, ON, Canada.

Child developmental theories and a large body of literature underscore the importance of both home and preschool influences on early childhood outcomes. We leveraged data from UNICEF'S Multiple Indicator Cluster Surveys, a nationally representative international household survey that has collected cohort comparable information on children's early development in over 118 low- and middle-income countries since 1995. We focused on data from 216,052 3- to 4-year-olds (106,037 girls) from 28 countries that had undertaken at least two surveys from 2010 to 2018. We considered the impact of maternal education and household wealth (what mothers/caregivers have) on home learning activities and sending children to early childhood programs (what mothers/caregivers do), on early child development. Our results indicated that maternal education, household wealth, home learning activities, participation in early childhood education (ECE) and scores on the early childhood development index (ECDI) generally increased over time and were significantly related to each other. Multilevel structural equation modeling revealed the mechanism through which maternal education and household wealth were associated with child outcomes. More wealthy and more educated mothers were more likely to send their child to an ECE program, which was in turn, associated with a higher ECDI score. Caregiver-reported participation in ECE had a large effect on the ECDI score while maternal education had a small effect on it. In comparison the effects of the home learning environment were much smaller. Taken together, findings suggest that education and wealth (what parents have) influence what they do (providing opportunities for learning), which in turn influences early child development. Furthermore, exposure to ECE services was particularly important for children's development. We conclude by discussing the policy implications of our findings and providing suggestions for future research.
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http://dx.doi.org/10.1016/bs.acdb.2021.04.002DOI Listing
June 2021

Decrease in abundance of bacteria of the genus in gut microbiota may be related to pre-eclampsia progression in women from East China.

Food Nutr Res 2021 28;65. Epub 2021 Jun 28.

Department of Obstetrics and Gynecology, Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Changzhou, China.

Background: Pre-eclampsia (PE) can result in severe damage to maternal and fetal health. It has been reported that gut microbiota (GM) had important roles in regulating the metabolic and inflammatory responses of the mother. However, investigations on GM in PE are rare.

Objective: The objective of the present study was to investigate the changes of GM in PE and how to alter the GM composition in PE by dietary or dietary supplements.

Design: We analyzed the composition changes in GM as well as the relationship between bacteria of different genera and clinical indices by amplifying the V4 region of the 16S ribosomal RNA gene in 12 PE patients and eight healthy pregnant women in East China.

Results: In the PE group, the Observed Species Index was lower than that in the control group, indicating that the α-diversity of the microbiome in the PE group decreased. At phylum, family, and genus levels, the relative abundance of different bacteria in PE patients displayed substantial differences to those from healthy women. We noted a decreased abundance of bacteria of the phylum Actinobacteria ( = 0.042), decreased abundance of bacteria of the family Bifidobacteriaceae ( = 0.039), increased abundance of bacteria of the genus ( = 0.026) and ( = 0.048), and decreased abundance of bacteria of the genus ( = 0.038) Among three enriched genera, bacteria of the genus showed a negative correlation with the systolic blood pressure (SBP), diastolic blood pressure (DBP), and dyslipidemia, which involved glucose metabolism, lipid metabolism, and the oxidative-phosphorylation pathway. The increased abundance of bacteria of the genera and was positively correlated with obesity and dyslipidemia, which involved lipid metabolism, glycosyltransferases, biotin metabolism, and the oxidative-phosphorylation pathways. Moreover, women in the PE group ate more than women in the control group, so fetuses were more prone to overnutrition in the PE group.

Conclusion: There is a potential for GM dysbiosis in PE patients, and they could be prone to suffer from metabolic syndrome. We speculate that alterations in the abundance of bacteria of certain genera (e.g. increased abundance of and , and decreased abundance of ) were associated with PE development to some degree. Our data could help to monitor the health of pregnant women and may be helpful for preventing and assisting treatment of PE by increasing dietary fiber or probiotics supplement.
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http://dx.doi.org/10.29219/fnr.v65.5781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254465PMC
June 2021

Genomic signatures supporting the symbiosis and formation of chitinous tube in the deep-sea tubeworm Paraescarpia echinospica.

Mol Biol Evol 2021 Jul 13. Epub 2021 Jul 13.

Department of Ocean Science and Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, Hong Kong, China.

Vestimentiferan tubeworms are iconic animals that present as large habitat-forming chitinised tube bushes in deep-sea chemosynthetic ecosystems. They are gutless and depend entirely on their endosymbiotic sulphide-oxidising chemoautotrophic bacteria for nutrition. Information on the genomes of several siboglinid endosymbionts has improved our understanding of their nutritional supplies. However, the interactions between tubeworms and their endosymbionts remain largely unclear due to a paucity of host genomes. Here, we report the chromosome-level genome of the vestimentiferan tubeworm Paraescarpia echinospica. We found that the genome has been remodelled to facilitate symbiosis through the expansion of gene families related to substrate transfer and innate immunity, suppression of apoptosis, regulation of lysosomal digestion and protection against oxidative stress. Furthermore, the genome encodes a programmed cell death pathway that potentially controls the endosymbiont population. Our integrated genomic, transcriptomic and proteomic analyses uncovered matrix proteins required for the formation of the chitinous tube and revealed gene family expansion and co-option as evolutionary mechanisms driving the acquisition of this unique supporting structure for deep-sea tubeworms. Overall, our study provides novel insights into the host's support system that has enabled tubeworms to establish symbiosis, thrive in deep-sea hot vents and cold seeps and produce the unique chitinous tubes in the deep sea.
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http://dx.doi.org/10.1093/molbev/msab203DOI Listing
July 2021

Comparative analysis of carbon footprint between conventional smallholder operation and innovative largescale farming of urban agriculture in Beijing, China.

PeerJ 2021 29;9:e11632. Epub 2021 Jun 29.

Department of Urban Planning and Design, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

The sustainable development of agriculture is one of the key issues of ensuring food security and mitigating climate change. Since innovative large-scale agriculture is gaining popularity in cities in China, where the agricultural landscape is dominated by conventional smallholder farming, it is necessary to investigate the difference in carbon emissions between conventional smallholder operation and innovative largescale agriculture. This study evaluated the carbon footprint (CF) of conventional and innovative urban agriculture in Beijing using the cradle-to-consumption Life Cycle Assessment (LCA). Two modes of greenhouse vegetable and fruit production were analyzed and compared respectively: conventional smallholder operated vegetable farms that sell in local markets versus largescale home-delivery agriculture (HDA) that deliver vegetables to consumers' home directly, conventional smallholder operated fruit farms that sell in farm shops versus largescale pick-your-own (PYO) initiatives. Results showed that HDA and PYO can reduce CF per area in on-farm cultivation compared to smallholder operation, while may bring an increase in CF per product weight unit and the gap was wider if the supply chain was considered. This is mainly because innovative large-scale farming consumes fewer agricultural inputs (e.g., fertilizer, pesticides) and obtains lower yields than conventional smallholder operations. Plastic materials with high carbon emission, fossil energy dependence and transportation efficiency are CF hotspots of both modes and therefore can be prioritized and targeted for carbon reduction adjustment. The results of this work further advance understanding of how innovative largescale agriculture and conventional smallholder operation compare and which particular inputs and activities should be prioritized to effectively reduce the CF in China during agricultural transformation.
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http://dx.doi.org/10.7717/peerj.11632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253110PMC
June 2021

[Comparison of the efficacy between open and arthroscopic Latarjet procedure in the treatment of anterior shoulder instability:a Meta-analysis].

Zhongguo Gu Shang 2021 Jun;34(6):573-83

The Forth Department of Joint, Wangjing Hospital of China Academy of Chinese Medical Science, Beijing 100102, China.

Objective: To compare the clinical efficacy between open and arthroscopic Latarjet procedure in the treatment of anterior shoulder instability by using Meta-analysis.

Methods: Search PubMed, Medline, Embase, Cochrane, China National Knowledge Infrastructure(CNKI), Wanfang database, China Biological Literature system(CBM) and VIP database. Review all retrospective or prospective cohort studies and randomized controlled trials on open and arthroscopic Latarjet procedure for anterior shoulder instability. Binary variables (postoperative recurrence rate, incidence of intraoperative and postoperative complications) and continuousvariables [shoulder external rotation range of motion, Walch-Duplay score, Rowe score, WOSI score, postoperative visual analogue scale (VAS), postoperative anxiety degree and operation time] were selected for analysis. NOS bias risk assessment criteria (recommended by Cochrane collaboration Network) were used to evaluate the literature quality of retrospective or prospective cohort studies, and modified Jadad scale was used to evaluate the quality of randomized controlled trials. Literature screening, literature quality evaluation and data extraction were carried out independently by two observers. RevMan 5.3 software was used for Meta analysis.

Results: (1)A total of 9 studies were included, including 8 retrospective cohort studies and 1 prospective cohort study. A total of 956 patients were included in this study, including open Latarjet procedure(=436) and arthroscopic Latarjet procedure(=520). (2)The postoperative WOSI score in the open group was better than that of arthroscopic group (=93.74, 95%:26.00 to 161.49, =0.007), and the α angle was smaller than arthroscopic group(=-6.44, 95%:-12.08 to 0.81, =0.02). (3)The recurrence rate of open Latarjet group was lower than that of arthroscopic Latarjet group, but there was no significant difference between the two groups (=0.84, 95%:0.23 to 3.05, =0.79). (4)There were no significant difference in shoulder external rotation, Walch-Duplay score, Rowe score, postoperative visual analogue score, postoperative anxiety degree and operation time between open and arthroscopic Latarjet group.

Conclusion: The arthroscopic Latarjet stabilisation shows satisfactory and comparable results to open procedure, and the postoperative recurrence and complication rates are low in both group. Both open and arthroscopic Latarjet procedure are reliable surgical procedures in the treatment of anteriorly shoulder instability. Arthroscopic procedure has longer learning curve than open procedure, the doctors may either choose arthroscopic or open Latarjet procedure based on personal skills and preference, as well as the patient's condition. However, all the literatures included in this study are cohort studies with low level of evidence. The research lack randomized controlled trials, and small sample size is small. In the future, randomized controlled studies with large sample size and high level of evidence are still needed to determine the efficacy difference between the two.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.06.019DOI Listing
June 2021

Influence of o,p'-DDT on Mucin 5 subtype A and C expression via regulation of NF-κB/AP-1 activation in human lung epithelial cells.

J Toxicol Environ Health A 2021 Jun 25:1-10. Epub 2021 Jun 25.

Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.

'-Dichlorodiphenyltrichloroethane ('-DDT) is a representative endocrine disruptor, and exposure to '-DDT may produce immune disorders and inflammation, leading to various diseases such as cancer. Chronic airway inflammation is characterized by excessive mucus secretion resulting in chronic obstructive pulmonary disease (COPD). Mucin 5AC  (MUC5AC), one of the mucus genes, plays an important role in mucus secretion and inflammation in the airways. The aim of this study was to examine the effects of '-DDT on the regulation of MUC5AC expression in human lung epithelial A549 cell line. '-DDT increased mRNA levels and the promoter activity of MUC5AC. Transient transfection with mutation promoter constructs of MUC5AC demonstrated that nuclear factor kappa-b (NF-κB) and activator protein 1(AP-1) response elements were essential for the consequences of -DDT on MUC5AC expression. In addition, '-DDT induced phosphorylation of ERK, JNK, p38, and Akt, which are involved in the regulation of MUC5AC expression. It is noteworthy that inhibitors of NF-κB, AP-1, Akt, and MAPKs blocked enhanced '-DDT-induced MUC5AC mRNA expression. Data indicate that '-DDT increase in NF-κB, and AP-1 transcriptional activation-dependent MUC5AC expression is associated with stimulation of Akt and MAPK signaling pathways in A549 cells.
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http://dx.doi.org/10.1080/15287394.2021.1944943DOI Listing
June 2021

Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?

Theranostics 2021 1;11(15):7471-7487. Epub 2021 Jun 1.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Immunotherapy provides a new avenue for combating cancer. Current research in anticancer immunotherapy is primary based on T cell-mediated cellular immunity, which can be divided into seven steps and is named the cancer-immunity cycle. Unfortunately, clinical applications of cancer immunotherapies are restricted by inefficient drug delivery, low response rates, and unmanageable adverse reactions. In response to these challenges, the combination of nanotechnology and immunotherapy (nano-immunotherapy) has been extensively studied in recent years. Rational design of advanced nano-immunotherapies requires in-depth consideration of "which" immune step is targeted, "why" it needs to be further enhanced, and "what" nanotechnology can do for immunotherapy. However, the applications and effects of nanotechnology in the cancer-immunity cycle have not been well reviewed. Herein, we summarize the current developments in nano-immunotherapy for each stage of cancer cellular immunity, with special attention on the which, why and what. Furthermore, we summarize the advantages of nanotechnology for combination immunotherapy in two categories: enhanced efficacy and reduced toxicity. Finally, we discuss the challenges of nano-immunotherapy in detail and provide a perspective.
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http://dx.doi.org/10.7150/thno.59953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210608PMC
July 2021

Measurement of the Brain Volume/Liver Volume Ratio by Three-Dimensional MRI in Appropriate-for-Gestational Age Fetuses and Those With Fetal Growth Restriction.

J Magn Reson Imaging 2021 Jun 21. Epub 2021 Jun 21.

Department of Radiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Fetal growth restriction (FGR) is associated with a high fetal brain volume/liver volume (FBV/FLV) ratio. Ultrasound may not always be reliable, which has prompted further investigation of MRI techniques.

Purpose: To determine the relationship between FBV/FLV ratio, as measured by MRI, and gestational age (GA) in normal fetuses and those with FGR.

Study Type: Retrospective.

Population: One hundred and forty seven singleton pregnancies including 105 appropriate-for-gestational age (AGA) fetuses and 42 FGR fetuses.

Field Strength/sequence: Three-dimensional fast imaging employing steady-state acquisition at 1.5 T.

Assessment: The FBV and FLV were measured by three radiologists. The inter- and intraobserver agreements, the correlation between FBV/FLV ratio, and advancing GA were evaluated; the diagnostic value of FBV/FLV ratio was evaluated and compared with head circumference/abdominal circumference (HC/AC) ratio measured by ultrasound.

Statistical Tests: Intraclass correlation coefficient (ICC) was used to determine inter- and intraobserver agreements. Regression analysis was used to assess the correlation between FBV/FLV ratio and advancing GA. The diagnostic value of the FBV/FLV ratio was examined by the area under the receiver operating characteristic (ROC) curve.

Results: The inter- and intraobserver agreements were excellent with an interobserver ICC of 0.984 and intra-observer ICCs of 0.989, 0.994, and 0.995. The FBV/FLV ratio in AGA fetuses decreased significantly with advancing GA (Pearson correlation coefficient = -0.844). The FBV/FLV ratio in FGR fetuses was significantly higher than that in AGA fetuses. To identify fetuses at high risk for FGR using the FBV/FLV ratio, the area under the ROC curve was 0.978, with an optimal cut-off value of 4.10. The sensitivity of FBV/FLV ratio in identifying FGR was significantly higher than that of HC/AC ratio (0.929 vs. 0.529).

Data Conclusion: An inverse correlation exists between FBV/FLV ratio and advancing GA in normal fetuses. A high FBV/FLV ratio may be used to ascertain fetuses at high risk for FGR.

Level Of Evidence: 3 Technical Efficacy Stage: 3.
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http://dx.doi.org/10.1002/jmri.27792DOI Listing
June 2021

Bacteria-Mediated Synergistic Cancer Therapy: Small Microbiome Has a Big Hope.

Nanomicro Lett 2021 Jan 4;13(1):37. Epub 2021 Jan 4.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People's Republic of China.

The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency. With dozens of clinical trials underway, some researchers hold the following views: "humans are nearing the first commercial live bacteria therapeutic." However, the facultative anaerobe Salmonella typhimurium VNP20009, which is particularly safe and shows anticancer effects in preclinical studies, had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects. This is almost certain to disappoint people's inflated expectations, but it is noted that recent state-of-the-art research has turned attention to bacteria-mediated synergistic cancer therapy (BMSCT). In this review, the foundation of bacteria-mediated bio-therapy is outlined. Then, we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities (chemotherapy, photothermal therapy, reactive oxygen and nitrogen species therapy, immunotherapy, or prodrug-activating therapy) in the past 5 years. Next, we discuss multiple administration routes of BMSCT, highlighting potentiated antitumor responses and avoidance of potential side effects. Finally, we envision the opportunities and challenges for BMSCT development, with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.
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http://dx.doi.org/10.1007/s40820-020-00560-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187705PMC
January 2021

The length of disulfide bond-containing linkages impacts the oral absorption and antitumor activity of paclitaxel prodrug-loaded nanoemulsions.

Nanoscale 2021 Jun;13(23):10536-10543

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

The rational design of oral paclitaxel (PTX) preparations is still a challenge. Many studies focus on developing PTX-loaded nanoemulsions (NEs) for oral administration. Unfortunately, PTX has poor affinity with the commonly used oil phases, leading to low encapsulation efficiency, poor colloidal stability, and premature drug leakage of PTX-loaded NEs. Herein, three lipophilic PTX prodrugs are synthesized by conjugating PTX with citronellol (CIT), using different lengths of disulfide bond-containing linkages. Interestingly, compared with PTX, the prodrugs exhibit higher affinity with the oil phase, effectively improving the encapsulation efficiency, colloidal stability, and sustained-release behavior of NEs. In addition, the disulfide bond-bridged prodrugs could specifically release PTX in tumor cells, reducing unnecessary systemic exposure of PTX. As a result, all three prodrug NEs exhibited improved oral bioavailability and antitumor effects compared to oral Taxol. Moreover, the length of disulfide bond-containing linkages exhibits great impacts on the oral absorption, drug release, and antitumor behaviors of NEs. It is found that the prodrug NEs with the shortest linkages show comparable antitumor effects with intravenous Taxol, but with less systemic and gastrointestinal toxicity.
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http://dx.doi.org/10.1039/d1nr01359aDOI Listing
June 2021

Characterization of Genes from and Its Function in Response to Dark-Induced Leaf Senescence.

Plants (Basel) 2021 May 10;10(5). Epub 2021 May 10.

College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China.

The Bcl-2-associated athanogene (BAG) family is a group of evolutionarily conserved cochaperones involved in diverse cellular functions. Here, ten putative genes were identified in tomato. and have the same gene structure and conserved domains, along with highly similar identity to their homologs in , , and . The qPCR data showed that and were highly expressed in stems and flowers. Moreover, both genes were differentially expressed under diverse abiotic stimuli, including cold stress, heat stress, salt treatment, and UV irradiation, and treatments with phytohormones, namely, ABA, SA, MeJA, and ETH. Subcellular localization showed that SlBAG2 and SlBAG5b were located in the cell membrane and nucleus. To elucidate the functions in leaf senescence of BAG2 and BAG5b, the full-length CDSs of and were cloned, and transgenic tomatoes were developed. Compared with WT plants, those overexpressing and had significantly increased chlorophyll contents, chlorophyll fluorescence parameters and photosynthetic rates but obviously decreased ROS levels, chlorophyll degradation and leaf senescence related gene expression under dark stress. Conclusively, overexpression and could improve the tolerance of tomato leaves to dark stress and delay leaf senescence.
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http://dx.doi.org/10.3390/plants10050947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151600PMC
May 2021

A computer-aided chem-photodynamic drugs self-delivery system for synergistically enhanced cancer therapy.

Asian J Pharm Sci 2021 Mar 17;16(2):203-212. Epub 2020 May 17.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

The therapeutic strategy that gives consideration to the combination of photodynamic therapy and chemotherapy, has emerged as a potential development of effective anti-cancer medicine. Nevertheless, co-delivery of photosensitizers (PSs) and chemotherapeutic drugs in traditional carriers still remains great limitations due to low drug loadings and poor biocompatibility. Herein, we have utilized a computer-aided strategy to achieve a desired carrier-free self-delivery of pyropheophorbide a (PPa, a common PS) and podophyllotoxin (PPT, a classical chemotherapeutic drug) for synergistic cancer therapy. First, the computational simulation method identified the similar molecular sizes and rigid molecular structures between two drugs molecules. Based on the molecular docking, the intermolecular interactions were found to include π-π stackings, hydrophobic interactions and hydrogen bonds. Next, both drugs could co-assemble into nanoparticles (NPs) via one-step nanoprecipitation method. The various spectral experiments (UV, IR and FL) were conducted to evaluate the formation mechanism of spherical NPs. Moreover, and experiments systematically demonstrated that PPT/PPa NPs not only showed better cellular uptake efficiency, stronger cytotoxicity and higher accumulation in tumor sites, but also exhibited synergistic antitumor effect in female BALB/C bearing-4T1 tumor mice. Such a computer-aided design strategy of chem-photodynamic drugs self-delivery systems pave the way for efficient synergistic cancer therapy.
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http://dx.doi.org/10.1016/j.ajps.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105418PMC
March 2021

Photosensitizer-driven nanoassemblies of homodimeric prodrug for self-enhancing activation and synergistic chemo-photodynamic therapy.

Theranostics 2021 7;11(12):6019-6032. Epub 2021 Apr 7.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, P. R. China.

Carrier-free prodrug-nanoassemblies have emerged as promising nanomedicines. In particular, the self-assembled nanoparticles (NPs) composed of homodimeric prodrugs with ultrahigh drug loading have attracted broad attention. However, most homodimeric prodrugs show poor self-assembly ability due to their symmetric structures. Herein, we developed photosensitizer-driven nanoassemblies of homodimeric prodrug for self-enhancing activation and chemo-photodynamic synergistic therapy. In this work, a pyropheophorbide a (PPa)-driven nanoassemblies of an oxidation-responsive cabazitaxel homodimer (CTX-S-CTX) was fabricated (pCTX-S-CTX/PPa NPs). The assembly mechanisms, aggregation-caused quenching (ACQ) effect alleviation, singlet oxygen generation, self-enhancing prodrug activation, cellular uptake, intracellular reactive oxygen species (ROS) generation and synergistic cytotoxicity of pCTX-S-CTX/PPa NPs were investigated . Moreover, the pharmacokinetics, biodistribution and therapeutic efficacy of pCTX-S-CTX/PPa NPs were studied in mice bearing 4T1 tumor. Interestingly, PPa was found to drive the assembly of CTX-S-CTX, which cannot self-assemble into stable NPs alone. Multiple intermolecular forces were found to be involved in the assembly process. Notably, the nanostructure was destroyed in the presence of endogenous ROS, significantly relieving the ACQ effect of PPa. In turn, ROS generated by PPa under laser irradiation together with the endogenous ROS synergistically promoted prodrug activation. As expected, the nanoassemblies demonstrated potent antitumor activity in a 4T1 breast cancer BALB/c mice xenograft model. Our findings offer a simple strategy to facilitate the assembly of homodimeric prodrugs and provide an efficient nanoplatform for chemo-photodynamic therapy.
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http://dx.doi.org/10.7150/thno.59065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058734PMC
July 2021

Unsaturated fatty acid-tuned assembly of photosensitizers for enhanced photodynamic therapy via lipid peroxidation.

J Control Release 2021 06 22;334:213-223. Epub 2021 Apr 22.

Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address:

Photodynamic therapy (PDT) destroys tumor cells mainly through singlet oxygen (O) generated by light-irradiated photosensitizers (PSs). However, the fleeting half-life of O greatly impairs PDT efficacy. Herein, we propose an unreported unsaturated fatty acid (UFA)-assisted PS co-assembly strategy to address this problem. Three UFAs, namely, oleic acid (OA), linoleic acid (LA) and linolenic acid (LNA), are capable of co-assembling with 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) into uniform nanoparticles. Under irradiation, TAPP produces O, which directly attacks tumor cells and simultaneously oxidizes UFAs to generate lipid hydroperoxides with sustained damage. Interestingly, the unsaturation degree of UFAs is not only related to their peroxidation rate but also has a remarkable impact on the intracellular TAPP release characteristic of the nanoparticles (NPs). The TAPP-LA NPs could release the cargo rapidly and produce the highest lipid peroxidation and reactive oxygen species levels upon irradiation. Such a unique finding sheds new light on UFA-based combination applications for enhanced photodynamic efficacy by boosting lipid peroxidation.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.022DOI Listing
June 2021

Differential Transcriptomes and Methylomes of Trophoblast Stem Cells From Naturally-Fertilized and Somatic Cell Nuclear-Transferred Embryos.

Front Cell Dev Biol 2021 1;9:664178. Epub 2021 Apr 1.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Trophoblast stem cells (TSCs) are critical to mammalian embryogenesis by providing the cell source of the placenta. TSCs can be derived from trophoblast cells. However, the efficiency of TSC derivation from somatic cell nuclear transfer (NT) blastocysts is low. The regulatory mechanisms underlying transcription dynamics and epigenetic landscape remodeling during TSC derivation remain elusive. Here, we derived TSCs from the blastocysts by natural fertilization (NF), NT, and a histone deacetylase inhibitor Scriptaid-treated NT (SNT). Profiling of the transcriptomes across the stages of TSC derivation revealed that fibroblast growth factor 4 (FGF4) treatment resulted in many differentially expressed genes (DEGs) at outgrowth and initiated transcription program for TSC formation. We identified 75 transcription factors (TFs) that are continuously upregulated during NF TSC derivation, whose transcription profiles can infer the time course of NF not NT TSC derivation. Most DEGs in NT outgrowth are rescued in SNT outgrowth. The correct time course of SNT TSC derivation is inferred accordingly. Moreover, these TFs comprise an interaction network important to TSC stemness. Profiling of DNA methylation dynamics showed an extremely low level before FGF4 treatment and gradual increases afterward. FGF4 treatment results in a distinct DNA methylation remodeling process committed to TSC formation. We further identified 1,293 CpG islands (CGIs) whose DNA methylation difference is more than 0.25 during NF TSC derivation. The majority of these CGIs become highly methylated upon FGF4 treatment and remain in high levels. This may create a barrier for lineage commitment to restrict embryonic development, and ensure TSC formation. There exist hundreds of aberrantly methylated CGIs during NT TSC derivation, most of which are corrected during SNT TSC derivation. More than half of the aberrantly methylated CGIs before NT TSC formation are inherited from the donor genome. In contrast, the aberrantly methylated CGIs upon TSC formation are mainly from the highly methylated CGIs induced by FGF4 treatment. Functional annotation indicates that the aberrantly highly methylated CGIs play a role in repressing placenta development genes, etc., related to post-implantation development and maintaining TSC pluripotency. Collectively, our findings provide novel insights into the transcription dynamics, DNA methylation remodeling, and the role of FGF4 during TSC derivation.
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http://dx.doi.org/10.3389/fcell.2021.664178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047118PMC
April 2021

Apoptotic body-mediated intercellular delivery for enhanced drug penetration and whole tumor destruction.

Sci Adv 2021 Apr 16;7(16). Epub 2021 Apr 16.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Chemotherapeutic nanomedicines can exploit the neighboring effect to increase tumor penetration. However, the neighboring effect is limited, likely by the consumption of chemotherapeutic agents and resistance of internal hypoxic tumor cells. Here, we first propose and demonstrate that apoptotic bodies (ApoBDs) could carry the remaining drugs to neighboring tumor cells after apoptosis. To enhance the ApoBD-based neighboring effect, we fabricated disulfide-linked prodrug nanoparticles consisting of camptothecin (CPT) and hypoxia-activated prodrug PR104A. CPT kills external normoxic tumor cells to produce ApoBDs, while PR104A remains inactive. The remaining drugs could be effectively delivered into internal tumor cells via ApoBDs. Although CPT exhibits low toxicity to internal hypoxic tumor cells, PR104A could be activated to exert strong cytotoxicity, which further facilitates deep penetration of the remaining drugs. Such a synergic approach could overcome the limitations of the neighboring effect to penetrate deep into solid tumors for whole tumor destruction.
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http://dx.doi.org/10.1126/sciadv.abg0880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051881PMC
April 2021

Poly(hexamethylene biguanide) (PHMB) as high-efficiency antibacterial coating for titanium substrates.

J Hazard Mater 2021 06 14;411:125110. Epub 2021 Jan 14.

Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, PR China; Jiangsu Engineering Research Center of Interfacial Chemistry, Nanjing University, Nanjing 210093, PR China. Electronic address:

Bacterial associated infection is a remaining urgent challenge in clinic application of metallic implants and devices. Here, we developed a new strategy to combat the bacterial associated infection of titanium alloy (TC4). Novel phosphonate/active ester block polymers (pDEMMP-b-pNHSMA) with identical phosphonate segments (DP = 29) as the metal anchorable ligand but varied active ester segments (DPs = 7, 29, and 64) as the conjugation site for poly(hexamethylene biguanide) (PHMB) were precisely prepared. Through a facile two-step process, the polymeric coating were successfully constructed on TC4 substrates as evidenced by water contact angle and XPS measurements. Through systematical in vitro antibacterial evaluations, robust relationship between the chemical structure of coating polymer and the antibacterial property endowed to the TC4 substrates has been established. Results showed that the block polymer, bearing an active ester segment of 64 repeat units, enabled dense packing of PHMB coating on the TC4 surface, which is able to kill 100% of both S. aureus and E. coli. that seeded without compromising the cytocompatibility of TC4 substrates. Furthermore, PHMB coating could significantly inhibit the colony of the bacteria and consequently reduce the bacterial associated inflammatory reaction as verified by a subcutaneous infection model on rat.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125110DOI Listing
June 2021

Melatonin Pretreatment Confers Heat Tolerance and Repression of Heat-Induced Senescence in Tomato Through the Modulation of ABA- and GA-Mediated Pathways.

Front Plant Sci 2021 25;12:650955. Epub 2021 Mar 25.

Key Laboratory of Southern Vegetable Crop Genetic Improvement in Ministry of Agriculture, College of Horticulture, Nanjing Agricultural University, Nanjing, China.

Heat stress and abscisic acid (ABA) induce leaf senescence, whereas melatonin (MT) and gibberellins (GA) play critical roles in inhibiting leaf senescence. Recent research findings confirm that plant tolerance to diverse stresses is closely associated with foliage lifespan. However, the molecular mechanism underlying the signaling interaction of MT with GA and ABA regarding heat-induced leaf senescence largely remains undetermined. Herein, we investigated putative functions of melatonin in suppressing heat-induced leaf senescence in tomato and how ABA and GA coordinate with each other in the presence of MT. Tomato seedlings were pretreated with 100 μM MT or water and exposed to high temperature (38/28°C) for 5 days (d). Heat stress significantly accelerated senescence, damage to the photosystem and upregulation of reactive oxygen species (ROS), generating gene expression. Melatonin treatment markedly attenuated heat-induced leaf senescence, as reflected by reduced leaf yellowing, an increased Fv/Fm ratio, and reduced ROS production. The gene, chlorophyll catabolic genes, and senescence-associated gene expression levels were significantly suppressed by MT addition. Exogenous application of MT elevated the endogenous MT and GA contents but reduced the ABA content in high-temperature-exposed plants. However, the GA and ABA contents were inhibited by paclobutrazol (PCB, a GA biosynthesis inhibitor) and sodium tungstate (ST, an ABA biosynthesis inhibitor) treatment. MT-induced heat tolerance was compromised in both inhibitor-treated plants. The transcript abundance of ABA biosynthesis and signaling genes was repressed; however, the biosynthesis genes MT and GA were upregulated in MT-treated plants. Moreover, GA signaling suppressor and catabolic gene expression was inhibited, while ABA catabolic gene expression was upregulated by MT application. Taken together, MT-mediated suppression of heat-induced leaf senescence has collaborated with the activation of MT and GA biosynthesis and inhibition of ABA biosynthesis pathways in tomato.
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http://dx.doi.org/10.3389/fpls.2021.650955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027311PMC
March 2021

MiR-3663-3p participates in the anti-hepatocellular carcinoma proliferation activity of baicalein by targeting SH3GL1 and negatively regulating EGFR/ERK/NF-κB signaling.

Toxicol Appl Pharmacol 2021 06 8;420:115522. Epub 2021 Apr 8.

National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710004, China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Xi'an, Shaanxi 710004, China; Center for Tumor and Immunology, the Precision Medical Institute, the Second Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710004, China. Electronic address:

Baicalein is a purified flavonoid that exhibits anticancer effects in hepatocellular carcinoma (HCC). However, its underlying molecular mechanisms remain largely unclear. In this study, we found that baicalein inhibited HCC cell growth, induced apoptosis, and blocked cell cycle arrest at the S phase in vitro, as well as reduced HCC tumor volume and weight in vivo. Quantitative reverse transcriptase-PCR (qRT-PCR) results suggested that miR-3663-3p was downregulated in HCC tissues. After baicalein treatment, miR-3663-3p expression was upregulated in HCC cells. Transfection of miR-3663-3p suppressed HCC cell proliferation and colony formation, increased the proportion of apoptotic cells in vitro, and reduced the volume and weight of tumors in vivo. The results of dual-luciferase reporter assay showed that miR-3663-3p could directly bind to the 3'-UTR of SH3GL1. SH3GL1 overexpression partly reduced the growth-inhibiting effect of miR-3663-3p. Both baicalein treatment and miR-3663-3p overexpression downregulated the expression of SH3GL1 and inactivated the Erk1/2, p-NF-κB/p65, and EGFR signaling pathways. Overall, our data suggest that baicalein may act as a novel HCC suppressor, and that the miR-3663-3p/SH3GL1/EGFR/ERK/NF-κB pathway plays a vital role in HCC progression. Thus, baicalein treatment or miR-3663-3p induction may be a promising strategy for HCC therapy.
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http://dx.doi.org/10.1016/j.taap.2021.115522DOI Listing
June 2021

Emerging nanotaxanes for cancer therapy.

Biomaterials 2021 05 1;272:120790. Epub 2021 Apr 1.

College of Pharmacy, Anhui University of Chinese Medicine and Anhui Academy of Chinese Medicine, Hefei, 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei, 230012, China. Electronic address:

The clinical application of taxane (including paclitaxel, docetaxel, and cabazitaxel)-based formulations is significantly impeded by their off-target distribution, unsatisfactory release, and acquired resistance/metastasis. Recent decades have witnessed a dramatic progress in the development of high-efficiency, low-toxicity nanotaxanes via the use of novel biomaterials and nanoparticulate drug delivery systems (nano-DDSs). Thus, in this review, the achievements of nanotaxanes-targeted delivery and stimuli-responsive nano-DDSs-in preclinical or clinical trials have been outlined. Then, emerging nanotherapeutics against tumor resistance and metastasis have been overviewed, with a particular emphasis on synergistic therapy strategies (e.g., combination with surgery, chemotherapy, radiotherapy, biotherapy, immunotherapy, gas therapy, phototherapy, and multitherapy). Finally, the latest oral nanotaxanes have been briefly discussed.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120790DOI Listing
May 2021

Molluscan phylogenomics requires strategically selected genomes.

Philos Trans R Soc Lond B Biol Sci 2021 May 5;376(1825):20200161. Epub 2021 Apr 5.

Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao 266003, People's Republic of China.

The extraordinary diversity in molluscan body plans, and the genomic mechanisms that enable it, remains one of the great questions of evolution. The eight distinct living taxonomic classes of molluscs are each unambiguously monophyletic; however, significant controversy remains about the phylogenetic relationships among those eight branches. Molluscs are the second-largest animal phylum, with over 100 000 living species with broad biological, economic and medical interest. To date, only around 53 genome assemblies have been accessioned to NCBI GenBank covering only four of the eight living molluscan classes. Furthermore, the molluscan taxa where partial or whole-genome assemblies are available are often aberrantly fast evolving or recently derived lineages. Characteristic adaptations provide interesting targets for whole-genome projects, in animals like the scaly-foot snail or octopus, but without basal-branching lineages for comparison, the context of recently derived features cannot be assessed. The currently available genomes also create a non-optimal set of taxa for resolving deeper phylogenetic branches: they are a small sample representing a large group, and those that are available come primarily from a rarefied pool. Thoughtful selection of taxa for future projects should focus on the blank areas of the molluscan tree, which are ripe with opportunities to delve into peculiarities of genome evolution, and reveal the biology and evolutionary history of molluscs. This article is part of the Theo Murphy meeting issue 'Molluscan genomics: broad insights and future directions for a neglected phylum'.
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http://dx.doi.org/10.1098/rstb.2020.0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059523PMC
May 2021
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