Publications by authors named "Ying Yin"

311 Publications

Overcoming Multidrug Resistance in Bacteria Through Antibiotics Delivery in Surface-Engineered Nano-Cargos: Recent Developments for Future Nano-Antibiotics.

Front Bioeng Biotechnol 2021 8;9:696514. Epub 2021 Jul 8.

Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou, China.

In the recent few decades, the increase in multidrug-resistant (MDR) bacteria has reached an alarming rate and caused serious health problems. The incidence of infections due to MDR bacteria has been accompanied by morbidity and mortality; therefore, tackling bacterial resistance has become an urgent and unmet challenge to be properly addressed. The field of nanomedicine has the potential to design and develop efficient antimicrobials for MDR bacteria using its innovative and alternative approaches. The uniquely constructed nano-sized antimicrobials have a predominance over traditional antibiotics because their small size helps them in better interaction with bacterial cells. Moreover, surface engineering of nanocarriers offers significant advantages of targeting and modulating various resistance mechanisms, thus owe superior qualities for overcoming bacterial resistance. This review covers different mechanisms of antibiotic resistance, application of nanocarrier systems in drug delivery, functionalization of nanocarriers, application of functionalized nanocarriers for overcoming bacterial resistance, possible limitations of nanocarrier-based approach for antibacterial delivery, and future of surface-functionalized antimicrobial delivery systems.
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http://dx.doi.org/10.3389/fbioe.2021.696514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297506PMC
July 2021

Latent Sex Differences in CaMKII-nNOS Signaling That Underlie Antidepressant-Like Effects of Yueju-Ganmaidazao Decoction in the Hippocampus.

Front Behav Neurosci 2021 6;15:640258. Epub 2021 Jul 6.

Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China.

Previous studies have demonstrated that Yueju-Ganmaidazao (YG) decoction induces rapid antidepressant-like effects, and the antidepressant response is mostly dependent on the suppression of nitric oxide-cyclic guanosine monophosphate signaling in male mice. This study aimed to investigate the sex difference mediated by calcium/calmodulin-dependent protein kinase II (CaMKII)-neuronal nitric oxide synthase (nNOS) signaling involved in the antidepressant-like effect of YG in mice. We found that the immobility times in the tail suspension test (TST) were found to be decreased after the single injection of YG in male and female mice with the same dosage. Additionally, chronic administration for 4 days of subthreshold dosage of YG and escitalopram (ES) also significantly decreased the immobility time in mice of both sexes. Chronic subthreshold dosage of YG and ES in LPS-treated mice and in chronic unpredictable stress (CUS) mice both decreased the immobility time, which was increased by stress. Meanwhile, in CUS-treated mice, sucrose preference test, forced swimming test, and open field test were applied to further confirm the antidepressant-like effects of YG and ES. Moreover, CUS significantly decreased the expression of nNOS and CaMKII, and both YG and ES could enhance the expression in the hippocampus of female mice, which was opposite to that in male mice, while endothelial nitric oxide synthase expression was not affected by stress or drug treatment neither in male mice nor in female mice. Finally, subthreshold dosage of YG combined with 7-nitroindazole (nNOS inhibitor) induced the antidepressant-like effects both in female and in male mice, while the single use of YG or 7-NI did not display any effect. However, pretreatment with KN-93 (CaMKII inhibitor) only blocked the antidepressant-like effect of high-dosage YG in female mice. Meanwhile, in CUS mice, chronic stress caused NR1 overexpression and inhibited cAMP response element binding protein action, which were both reversed by YG and ES in male and female mice, implying that YG and ES produced the same antidepressant-like effect in mice of both sexes. The study revealed that chronic treatment with a subthreshold dose of YG also produced antidepressant-like effects in female mice, and these effects depended on the regulation of the CaMKII-nNOS signaling pathway.
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http://dx.doi.org/10.3389/fnbeh.2021.640258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290083PMC
July 2021

Comparison of S-1-based vs. capecitabine-based adjuvant chemotherapy for patients with gastric cancer: a systematic review and meta-analysis.

Eur J Clin Pharmacol 2021 Jul 17. Epub 2021 Jul 17.

The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Zhejiang Province, Hangzhou, People's Republic of China.

Background: S-1-based and capecitabine-based adjuvant treatments are proved efficacious for patients with gastric cancer, but conventional meta-analyses of the direct comparisons between two alternative adjuvant regimens to resection of GC have not been attempted.

Aim: The aim of this review was to compare the disease-free survival, overall survival and adverse events in patients receiving the S-1- and capecitabine-based adjuvant chemotherapies for treatment of gastric cancer (GC) patients undergoing resection.

Methods: A search of the academic literature was performed in PUBMED, SCOPUS, CENTRAL and EMBASE databases along with manual search in relevant journals for studies in English, to identify comparative studies comparing the effect of S-1-based chemotherapy and capecitabine-based adjuvant chemotherapy (AC), used in combination with surgical resection for treatment of gastric cancer. Both qualitative and quantitative analyses was carried out for all the included studies. The hazard ratios (HR) of disease-free survival (DFS) and overall survival (OS) were pooled using generic inverse variance method. The included studies were assessed for risk of bias using ROBINS-E (risk of bias in non-randomized studies of exposures) tool.

Results: Seven retrospective cohort studies, two prospective cohort studies and one randomized clinical trial were included. Both S-1- and capecitabine-based adjuvant chemotherapy for treatment of stage 2 or 3 gastric cancer had similar effects on the 3-year and 5-year DFS rates, overall survival and adverse events in the included studies. There was no difference in the adjusted hazard ratios (HR) of OS and DFS (0.86 95% CI (0.68, 1.09); p = 0.21 and 0.96 95% CI (0.75, 1.24), respectively). Oral mucositis was increasingly associated with S-1-based AC, while incidences of adverse events such as neutropenia, anaemia and thrombocytopenia were similar to those of capecitabine-based regimen. The quality of the included studies was found to be low to moderate.

Conclusion: S-1- and capecitabine-based adjuvant chemotherapies can be used interchangeably as an adjuvant chemotherapeutic regimen postradical gastrectomy with D2 lymph node dissection.
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http://dx.doi.org/10.1007/s00228-021-03187-wDOI Listing
July 2021

A novel permeable reactive biobarrier for ortho-nitrochlorobenzene pollution control in groundwater: Experimental evaluation and kinetic modelling.

J Hazard Mater 2021 Jul 3;420:126563. Epub 2021 Jul 3.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China; Joint International Research Centre for Critical Zone Science-University of Leeds and Nanjing University, Nanjing University, Nanjing 210023, China. Electronic address:

Three novel permeable reactive barrier (PRB) materials composed of Cu/Fe with 0.24% and 0.43% (w/w) Cu loadings or Fe supported on wheat straw were prepared (termed materials E, F and G). These materials exhibited excellent pollutant removal efficiency and physical stability as well as the ongoing release of organic carbon and iron. Column experiments showed that materials E, F and G removed almost 100% of ortho-nitrochlorobenzene (o-NCB) from water. The rates of iron release from the E and F columns exceeded those from column G but this had no significant effect on o-NCB removal. The bacteria that degraded o-NCB in E and F were also different from those in G. The levels of these bacteria in the columns were higher than those in the initial materials, with the highest level in column E. The simultaneous reduction and microbial degradation of o-NCB was observed, with the latter being dominant. A kinetic model was established to simulate the dynamic interactions and accurately predicted the experimental results. Organic carbon from the wheat straw supported the majority of the biomass in each column, which was essential for the bioremediation process. The findings of this study suggest an economically viable approach to mitigating o-NCB pollution.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126563DOI Listing
July 2021

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Chin Med Sci J 2021 Jun;36(2):103-109

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene () polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 μmol/L) (=0.006), while no effect of gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 μmol/L) (=0.491). Conclusion The C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.
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http://dx.doi.org/10.24920/003792DOI Listing
June 2021

Impact of biochar-induced vertical mobilization of dissolved organic matter, sulfamethazine and antibiotic resistance genes variation in a soil-plant system.

J Hazard Mater 2021 09 25;417:126022. Epub 2021 May 25.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China; Joint International Research Centre for Critical Zone Science-University of Leeds and Nanjing University, Nanjing University, Nanjing 210023, China. Electronic address:

The migration risk of antibiotic and antibiotic resistance genes (ARGs) have attracted lots of attentions due to their potential threaten to public health. Strategies to reduce their vertical mobilization risk are urgently required for groundwater safety and human health. Biochar enjoys numerous interests due to its excellent sorption affinity. However, little was known about the efficacy of biochar amendment in impeding the vertical mobilization of antibiotic and ARGs. To fill this gap, a column study was carried out to investigate biochar-induced variations in the leaching behavior of dissolved organic matter (DOM), sulfamethazine (SMZ) and ARGs. Results showed that biochar addition enhanced DOM export from soil, changed its composition and impeded the vertical transport of SMZ. Biochar amendment could effectively decrease the occurrence of extracellular and intracellular sul2 in soil and impede its vertical transportation, however, it did not work out with sul1 gene. Structural equation modeling analysis demonstrated that the abundance of sul2 was significantly controlled by SMZ concentration, while the primary drivers of sul1 were SMZ concentration and DOM content. These results indicated the failure in inhibiting the vertical transfer of sul1 under biochar amendment and highlighted the important role of DOM in the leaching of soil ARGs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126022DOI Listing
September 2021

Insights into the mechanism of the interference of sulfadiazine on soil microbial community and function.

J Hazard Mater 2021 Jun 10;419:126388. Epub 2021 Jun 10.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China; Joint International Research Centre for Critical Zone Science-University of Leeds and Nanjing University, Nanjing University, Nanjing 210023, China. Electronic address:

The accumulation of sulfonamides in the soil environment possessed the potential to change soil microbial community and function. Metabolomics is capable of providing insights into the carbon metabolic pool and molecular mechanisms associated with external stressors. Here we evaluated alternations in soil bacterial community and soil metabolites profiles under sulfadiazine (SDZ) exposure and proposed a potential mechanism that SDZ accumulation in soil affected soil organic matter (SOM) cycling. Sequencing analysis showed that the relative abundance of bacterial species associated with carbon cycling significantly decreased under high concentrations of SDZ exposure. Untargeted metabolomics analysis showed that 78 metabolites were significantly changed with the presence of SDZ in soil. The combination of functional predictions and pathway analysis both demonstrated that high concentrations of SDZ exposure could cause disturbance in anabolism and catabolism. Moreover, the noticeable decline in the relative content of carbohydrates under high concentrations of SDZ exposure might weaken physical separation and provide more chances for microbes to degrade SOM. The above results provided evidence that SDZ accumulation in soil held the potential to disturb SOM cycling. These findings spread our understanding about the environmental risk of antibiotic in the soil environment beyond the dissemination of antibiotic resistance.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126388DOI Listing
June 2021

Integrated Assessment of Cd-contaminated Paddy Soil with Application of Combined Ameliorants: A Three-Year Field Study.

Bull Environ Contam Toxicol 2021 Jun 23. Epub 2021 Jun 23.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, 210023, Nanjing, China.

Cadmium accumulation in rice is a major source of Cd exposure in humans worldwide. A three-year field experiment was conducted to investigate the ecological safety and long-term stability of biochar combined with lime or silicon fertilizer for Cd immobilization in a polluted rice paddy. The results showed that the application of combined ameliorants could reduce the Cd content in brown rice to meet the Chinese maximum permissible limit for Cd content in food products (0.2 mg/kg). In addition, such amendments stimulated metabolic pathways in soil bacteria, including carbon metabolism, citrate cycle, pyruvate metabolism, biosynthesis of amino acids, and glycolysis/gluconeogenesis, revealing improvements in soil biological activity and soil health. Therefore, the results provide a practical strategy for the safe utilization of farmland with mild levels of heavy metal pollution.
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http://dx.doi.org/10.1007/s00128-021-03289-2DOI Listing
June 2021

Reward mechanism of depressive episodes in bipolar disorder: Enhanced theta power in feedback-related negativity.

J Affect Disord 2021 09 29;292:217-222. Epub 2021 May 29.

Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address:

Introduction: This study aimed to explore the reward-related neural mechanism in patients with depressive mood in bipolar disorder (BD) using event-related potentials. It remains unknown whether or not different neurobiological markers underlying depression symptoms in BD depression and major depression disorder (MDD).

Methods: 24 patients with BD depression and 20 healthy controls were included. Participants underwent evaluation with the Temporal Experience of Pleasure Scale (TEPS), followed by the classical gambling paradigm, while undergoing 64-channel electroencephalography. The waveform of feedback-related negativity (FRN) was extracted from the 250-350 ms time-window after participants received feedback regarding loss or gain. Event-related potential datasets were obtained using time-frequency analysis.

Results: (1) The TEPS scores of the patients were significantly lower than those of the controls [t = 5.16, p < 0.01]. (2) The event of loss elicited a deeper FRN in patients than that in controls [t = 2.19, p < 0.05], while no difference was observed in the event of gains (t = 1.12, p > 0.05). (3) Theta power rooted in FRN in patients was significantly higher in loss than in gain [F = 30.32, p < 0.01]. (4) Analysis of Variance (ANOVA) illustrated the interaction effect of theta power in gain/loss between two groups [F = 3.59, p = 0.06].

Limitation: Our study did not analyze the effect of different drugs which might affect our results.

Conclusion: The enhanced reflection of negative feedback was consistent with the negative bias, impulse control impairment, and emotional dysregulation observed in the bipolar disorder spectrum. We suggested that the extreme theta power generated from the anterior cingulate gyrus (ACC) might be the main component of abnormal FRN.
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http://dx.doi.org/10.1016/j.jad.2021.05.057DOI Listing
September 2021

Conservative production of galactosaminogalactan in Metarhizium is responsible for appressorium mucilage production and topical infection of insect hosts.

PLoS Pathog 2021 Jun 14;17(6):e1009656. Epub 2021 Jun 14.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

The exopolysaccharide galactosaminogalactan (GAG) has been well characterized in Aspergilli, especially the human pathogen Aspergillus fumigatus. It has been found that a five-gene cluster is responsible for GAG biosynthesis in Aspergilli to mediate fungal adherence, biofilm formation, immunosuppression or induction of host immune defences. Herein, we report the presence of the conserved GAG biosynthetic gene cluster in the insect pathogenic fungus Metarhizium robertsii to mediate either similar or unique biological functions. Deletion of the gene cluster disabled fungal ability to produce GAG on germ tubes, mycelia and appressoria. Relative to the wild type strain, null mutant was impaired in topical infection but not injection of insect hosts. We found that GAG production by Metarhizium is partially acetylated and could mediate fungal adherence to hydrophobic insect cuticles, biofilm formation, and penetration of insect cuticles. In particular, it was first confirmed that this exopolymer is responsible for the formation of appressorium mucilage, the essential extracellular matrix formed along with the infection structure differentiation to mediate cell attachment and expression of cuticle degrading enzymes. In contrast to its production during A. fumigatus invasive growth, GAG is not produced on the Metarhizium cells harvested from insect hemocoels; however, the polymer can glue germ tubes into aggregates to form mycelium pellets in liquid culture. The results of this study unravel the biosynthesis and unique function of GAG in a fungal system apart from the aspergilli species.
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http://dx.doi.org/10.1371/journal.ppat.1009656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224951PMC
June 2021

Increasing the Ascomycin Yield by Relieving the Inhibition of Acetyl/Propionyl-CoA Carboxylase by the Signal Transduction Protein GlnB.

Front Microbiol 2021 26;12:684193. Epub 2021 May 26.

Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China.

Ascomycin (FK520) is a multifunctional antibiotic produced by var. . In this study, we demonstrated that the inactivation of GlnB, a signal transduction protein belonging to the PII family, can increase the production of ascomycin by strengthening the supply of the precursors malonyl-CoA and methylmalonyl-CoA, which are produced by acetyl-CoA carboxylase and propionyl-CoA carboxylase, respectively. Bioinformatics analysis showed that var. contains two PII family signal transduction proteins, GlnB and GlnK. Protein co-precipitation experiments demonstrated that GlnB protein could bind to the α subunit of acetyl-CoA carboxylase, and this binding could be disassociated by a sufficient concentration of 2-oxoglutarate. Coupled enzyme activity assays further revealed that the interaction between GlnB protein and the α subunit inhibited both the activity of acetyl-CoA carboxylase and propionyl-CoA carboxylase, and this inhibition could be relieved by 2-oxoglutarate in a concentration-dependent manner. Because GlnK protein can act redundantly to maintain metabolic homeostasis under the control of the global nitrogen regulator GlnR, the deletion of GlnB protein enhanced the supply of malonyl-CoA and methylmalonyl-CoA by restoring the activity of acetyl-CoA carboxylase and propionyl-CoA carboxylase, thereby improving the production of ascomycin to 390 ± 10 mg/L. On this basis, the co-overexpression of the β and ε subunits of propionyl-CoA carboxylase further increased the ascomycin yield to 550 ± 20 mg/L, which was 1.9-fold higher than that of the parent strain FS35 (287 ± 9 mg/L). Taken together, this study provides a novel strategy to increase the production of ascomycin, providing a reference for improving the yield of other antibiotics.
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http://dx.doi.org/10.3389/fmicb.2021.684193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187598PMC
May 2021

Unicentric Castleman's disease of hepatic hilum and retroperitoneum: a case report for endoscopic ultrasonography differential diagnosis and a literature review.

Clin J Gastroenterol 2021 Aug 10;14(4):1250-1254. Epub 2021 Jun 10.

Department of Gastroenterology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.

Castleman's disease (CD) is a highly heterogeneous clinico-pathological entity belonging to the lymphoproliferative disorders. CD can occur in any part of the human body where lymph nodes are present. In addition, very few cases have been reported in hepatic hilum. Here, we present a case of a middle-aged female patient who was presented with abdominal pain and diagnosed as localized Castleman's disease of hepatic hilar and retroperitoneal origin. Diagnosing CD is complex due to its resemblance to many other diseases. EUS and FNA may play a more important role in differential diagnosis of CD and other disease in digestive system.
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http://dx.doi.org/10.1007/s12328-021-01418-2DOI Listing
August 2021

Predictive Factor of Large-Volume Central Lymph Node Metastasis in Clinical N0 Papillary Thyroid Carcinoma Patients Underwent Total Thyroidectomy.

Front Oncol 2021 19;11:574774. Epub 2021 May 19.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Large-volume central lymph node metastasis (large-volume CLNM) is associated with high recurrence rate in papillary thyroid carcinoma (PTC) patients. However, sensitivity in investigating large-volume CLNM on preoperative ultrasonography (US) is not high. The aim of this study is to investigate the clinical factors associated with large-volume CLNM in clinical N0 PTC patients. We reviewed 976 PTC patients undergoing total thyroidectomy with central lymph node dissection during 2017 to 2019. The rate of large-volume LNM was 4.1% (40 of 967 patients). Multivariate analysis showed that male gender and young age (age<45 years old) were independent risk factors for large-volume CLNM with odds ratios [(OR), 95% confidence interval (CI)] of 2.034 (1.015-4.073) and 2.997 (1.306-6.876), respectively. In papillary thyroid microcarcinoma (PTMC), capsule invasion was associated with large-volume CLNM with OR (95% CI) of 2.845 (1.110-7.288). In conventional papillary thyroid cancer (CPTC), tumor diameter (>2cm) was associated with large-volume CLNM, with OR (95% CI) 3.757 (1.061-13.310), by multivariate analysis. In ROC curve analysis on the diameter of the CPTC tumor, the Area Under Curve (AUC) =0.682(p=0.013), the best cut-off point was selected as 2.0cm. In conclusion, male gender and young age were predictors for large-volume CLNM of cN0 PTC. cN0 PTMC patient with capsule invasion and cN0 CPTC patient with tumor diameter >2cm were correlated with large-volume CLNM. Total thyroidectomy with central lymph node dissection may be a favorable primary treatment option for those patients.
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http://dx.doi.org/10.3389/fonc.2021.574774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170408PMC
May 2021

Screening of potential vaccine candidates against pathogenic Brucella spp. using compositive reverse vaccinology.

Vet Res 2021 Jun 2;52(1):75. Epub 2021 Jun 2.

Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, China.

Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.
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http://dx.doi.org/10.1186/s13567-021-00939-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170439PMC
June 2021

Research on Optimization of Healthcare Waste Management System Based on Green Governance Principle in the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 05 17;18(10). Epub 2021 May 17.

School of Economics and Management, China University of Geosciences, Wuhan 430074, China.

At present, strategies for controlling the COVID-19 pandemic have made significant and strategic strides; however, and the large quantities of healthcare treatment waste have become another important "battlefield". For example, in Wuhan, the production rate of healthcare waste in hospitals, communities, temporary storage, and other units was much faster than the disposal rate during the COVID-19 pandemic. Improving the efficiency of healthcare waste transfer and treatment has become an important task for government health and environmental protection departments at all levels. Based on the situation of healthcare waste disposal in Wuhan during the critical period of the pandemic, this paper analyzes and studies green governance principles and summarizes the problems that exist in the current healthcare waste management system. Through the establishment of temporary storage facilities along transit routes, digital simulation and bionic experiments were carried out in the Hongshan District of Wuhan to improve the efficiency of healthcare waste transfer. Furthermore, this study discusses the coordination and cooperation of government, hospitals, communities, and other departments in the healthcare waste disposal process and provides guiding suggestions for healthcare waste disposal nationwide in order to deal with potential risks and provide effective references in all regions.
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http://dx.doi.org/10.3390/ijerph18105316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156784PMC
May 2021

Gut Microbiota May Not Be Fully Restored in Recovered COVID-19 Patients After 3-Month Recovery.

Front Nutr 2021 13;8:638825. Epub 2021 May 13.

Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Coronavirus disease 2019 (COVID-19) has infected over 124 million people worldwide. In addition to the development of therapeutics and vaccines, the evaluation of the sequelae in recovered patients is also important. Recent studies have indicated that COVID-19 has the ability to infect intestinal tissues and to trigger alterations of the gut microbiota. However, whether these changes in gut microbiota persist into the recovery stage remains largely unknown. Here, we recruited seven healthy Chinese men and seven recovered COVID-19 male patients with an average of 3-months after discharge and analyzed their fecal samples by 16S rRNA sequencing analysis to identify the differences in gut microbiota. Our results suggested that the gut microbiota differed in male recovered patients compared with healthy controls, in which a significant difference in Chao index, Simpson index, and β-diversity was observed. And the relative abundance of several bacterial species differed clearly between two groups, characterized by enrichment of opportunistic pathogens and insufficiency of some anti-inflammatory bacteria in producing short chain fatty acids. The above findings provide preliminary clues supporting that the imbalanced gut microbiota may not be fully restored in recovered patients, highlighting the importance of continuous monitoring of gut health in people who have recovered from COVID-19.
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http://dx.doi.org/10.3389/fnut.2021.638825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155354PMC
May 2021

Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease.

J Med Chem 2021 06 23;64(11):7483-7506. Epub 2021 May 23.

State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.

Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC = 51.1 nM; GSK-3β: IC = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00160DOI Listing
June 2021

Merging N-Hydroxyphthalimide into Metal-Organic Frameworks for Highly Efficient and Environmentally Benign Aerobic Oxidation.

Chemistry 2021 Jul 1;27(37):9674-9685. Epub 2021 Jun 1.

Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P. R. China.

Two highly efficient metal-organic framework catalysts TJU-68-NHPI and TJU-68-NDHPI have been successfully synthesized through solvothermal reactions of which the frameworks are merged with N-hydroxyphthalimide (NHPI) units, resulting in the decoration of pore surfaces with highly active nitroxyl catalytic sites. When t-butyl nitrite (TBN) is used as co-catalyst, the as-synthesized MOFs are demonstrated to be highly efficient and recyclable catalysts for a novel three-phase heterogeneous oxidation of activated C-H bond of primary and secondary alcohols, and benzyl compounds under mild conditions. Based on the high efficiency and selectivity, an environmentally benign system with good sustainability, mild conditions, simple work-up procedure has been established for practical oxidation of a wide range of substrates.
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http://dx.doi.org/10.1002/chem.202100987DOI Listing
July 2021

Effects of polystyrene microplastic on uptake and toxicity of copper and cadmium in hydroponic wheat seedlings (Triticum aestivum L.).

Ecotoxicol Environ Saf 2021 Jul 13;217:112217. Epub 2021 Apr 13.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.

Microplastics are widespread in freshwater environments, their biological effects and combined effects of other pollutants have attracted extensive attention. In this study, we investigated the adsorption properties of heavy metals onto polystyrene (PS) microplastics as well as the bioavailability and toxicity of microplastics and heavy metals by hydroponic wheat seedlings experiment. Results showed that PS microplastics (0.5 µm, 100 mg/L) had no significant effect on wheat seedlings growth, photosynthesis, and reactive oxygen species (ROS) content. However, PS microplastics could adsorb copper and cadmium, with a predominantly chemisorption. The accumulation of copper and cadmium in wheat seedlings reduced in the presence of PS microplastics, which meant the toxic effect by heavy metals might be mitigated. Compared with single heavy metals treatments, the combination of PS microplastics and heavy metals increased chlorophyll content, enhanced photosynthesis and reduced the accumulation of ROS. These findings suggest that PS microplastics (0.5 µm, 100 mg/L) have a mitigating effect on the bioavailability and toxicity of copper and cadmium.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112217DOI Listing
July 2021

Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy.

Biomaterials 2021 06 31;273:120784. Epub 2021 Mar 31.

School of Medicine, Chongqing University, Chongqing, 400044, China; Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China. Electronic address:

Clinical treatment of malignant glioma remains a major challenge due to high infiltrative growth and chemotherapeutic resistance of tumors and the presence of the blood brain barrier (BBB). Advanced nanoplatforms that can efficiently cross the BBB and target to brain tumor are urgently needed. Encouraged by the intrinsic inflammatory chemotaxis and excellent BBB-crossing capability of neutrophils, a bioinspired neutrophil-exosomes (NEs-Exos) system for delivering loaded doxorubicin (DOX) drug for glioma treatment is proposed and systematically investigated. In vivo zebrafish and C6-Luc glioma-bearing mice models show that NEs-Exos carrying the drug rapidly penetrate the BBB and migrate into the brain. Additionally, a transwell BBB model and mouse brain inflammatory study show that NEs-Exos can respond chemotactically to inflammatory stimuli and target infiltrating tumor cells in inflamed brain tumors. Moreover, intravenous injection of NEs-Exos/DOX efficiently suppress tumor growth and prolong survival time in a glioma mouse model. On the basis of these results, NEs-Exos are confirmed to have neutrophil-like chemotactic function and BBB penetration. This novel NEs-Exos/DOX delivery platform represents a promising chemotherapeutic approach for clinical treatment of glioma and other solid tumor or brain diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120784DOI Listing
June 2021

STAT5 inhibitor attenuates atherosclerosis via inhibition of inflammation: the role of STAT5 in atherosclerosis.

Am J Transl Res 2021 15;13(3):1422-1431. Epub 2021 Mar 15.

Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine Hangzhou 310012, Zhejiang, China.

Atherosclerosis is a chronic inflammatory disease driven by lipids, which occurs preferentially in the branches or curved areas of the middle and large arteries, contributing to increased morbidity and mortality of cardiovascular disease. Recently, it has been reported that STAT5 and its regulated immune response are closely related to non-tumor diseases. However, the role of STAT5 in the development of atherosclerosis remains unknown. In this study, atherosclerosis was induced by high-fat diet (HFD) in ApoE mice, and STAT5-IN-1, a STAT5 inhibitor, was orally given. Macrophages stimulated by oxLDL were used as cell models . The effects of STAT5-IN-1 in ApoE mice induced by HFD were assessed, and the underlying mechanisms were investigated by siRNA-induced gene silencing. The results revealed that treatment with STAT5 inhibitor significantly attenuated atherosclerosis in ApoE mice induced by HFD via decreasing inflammation. Furthermore, it was demonstrated that inhibiting STAT5 could decrease oxLDL-induced inflammation. In summary, STAT5-IN-1 may be a potential drug for the treatment of atherosclerosis, and targeting STAT5 has the ability to be a potential therapeutic strategy for reducing atherosclerosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014372PMC
March 2021

Concurrent validity of the short version of Montreal Cognitive Assessment (MoCA) for patients with stroke.

Sci Rep 2021 Mar 30;11(1):7204. Epub 2021 Mar 30.

Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The aim of the present study was to examine the concurrent validity of 2 Chinese versions of the short version of the Montreal Cognitive Assessment (MoCA) in patients with stroke, i.e., MoCA 5-minute protocol and National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) 5-minute Protocol. A total of 54 patients and 27 healthy controls were enrolled in this study. In this study, the Neurobehavioural Cognitive Status Examination (NCSE) was used as an external criterion of cognitive impairment. We found that the 5-min protocol did not differ from the MoCA in differentiating patients with cognitive impairments from those without (area under the receiver operating characteristic curve, AUC, of 0.948 for the MoCA 5-min protocol v.s. 0.984 for MoCA, P = 0.097). These three assessments demonstrated equal performance in differentiating patients with stroke from controls. The Chinese version of the MoCA 5-min protocol can be used as a valid screening for patients with stroke.
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http://dx.doi.org/10.1038/s41598-021-86615-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010108PMC
March 2021

Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression.

Inflammation 2021 Jun 10;44(3):1160-1174. Epub 2021 Mar 10.

Department of Anesthesiology, Anhui Provincial Hospital, Cheeloo College of Medicine, Shangdong University, 17 Lujiang Road, Hefei, 230000, Anhui, China.

Liver ischemia-reperfusion (I/R) injury is a pathological process that often occurs during liver and trauma surgery. This study aimed to investigate the protective effect and potential mechanisms of sufentanil on hepatic I/R injury. I/R rat model and hypoxic/reoxygenation (H/R)-induced buffalo rat liver (BRL)-3A cell model were established. Following pretreatment with sufentanil, the enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rat serum and the changes of hepatic histopathology were evaluated to track the extent of liver injury. The levels of inflammatory factors were determined with ELISA kits and RT-qPCR. The infiltration of macrophages was assessed after detecting monocyte chemoattractant protein 1 (MCP-1) and F4/80 expression. Additionally, apoptosis was measured by means of TUNEL staining, and gene expression related to apoptosis was examined using RT-qPCR and western blotting. Then, TP53BP2 was overexpressed in BRL-3A cells exposed to H/R condition to evaluate whether sufentanil defended the liver against injury by regulating TP53BP2 expression. Moreover, the potential binding site of ATF4 on the TP53BP2 promoter was analyzed using JASPAR databases and verified by chromosomal immunoprecipitation (ChIP) assay. Furthermore, TP53BP2 expression and endoplasmic reticulum stress (ERS)-related protein levels were determined after ATF4 was overexpressed in sufentanil-treated BRL-3A cells. Results revealed that sufentanil significantly improved hepatic I/R injury, decreased the levels of inflammatory factors, and alleviated hepatocyte apoptosis. Notably, upregulated TP53BP2 expression was observed in hepatic tissues, and TP53BP2 overexpression markedly reversed the protective effects of sufentanil on the inflammation and apoptosis in H/R-stimulated BRL-3A cells. Additionally, ATF4 was confirmed to combine with the TP53BP2 promoter. ATF4 upregulation attenuated the inhibitory effects of sufentanil on the expression of TP53BP2 and ERS-associated proteins. These findings demonstrated that sufentanil protects the liver from inflammation and apoptosis injury induced by I/R by inhibiting ATF4 expression and further suppressing TP53BP2 expression, suggesting a promising therapeutic candidate for the treatment of liver I/R injury.
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http://dx.doi.org/10.1007/s10753-020-01410-xDOI Listing
June 2021

Risk Factors for Central and Lateral Lymph Node Metastases in Patients With Papillary Thyroid Micro-Carcinoma: Retrospective Analysis on 484 Cases.

Front Endocrinol (Lausanne) 2021 5;12:640565. Epub 2021 Mar 5.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Papillary thyroid micro-carcinoma (PTMC) is defined as a tumor with a larger diameter ≤1 cm which has an indolent course and satisfying prognosis. However, the incidence of lymph node metastasis of PTMC cannot be ignored. The aim of this study was to assess the incidence of lymph node metastasis in PTMC patients, as well as to evaluate the risk factors for both central lymph node metastases (CLNM) and lateral lymph node metastases (LLNM).

Methods: Patients who underwent thyroidectomy from January 2017 to October 2020, and pathologically diagnosed with PTMC were enrolled in our study and their medical records were collected and analyzed.

Results: A total of 484 PTMC patients were included. The incidence of central and lateral lymph node metastasis was 49.6% and 9.1%, respectively. Multivariate analysis demonstrated as independent risk factors for CLNM male sex, age <40 years, largest tumor size ≥5 mm and bilaterality. Extrathyroidal extension, presence of CLNM, number of CLNM ≥5 were strong indicators for LLNM.

Conclusion: The incidence of lymph node metastases in PTMC is non-negligible. The identification of potential risk factors for CLNM and LLNM would help tailor individual surgical interventions for patients with PTMC.
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http://dx.doi.org/10.3389/fendo.2021.640565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973362PMC
March 2021

Bmi1 regulate tooth and mandible development by inhibiting p16 signal pathway.

J Cell Mol Med 2021 May 21;25(9):4195-4203. Epub 2021 Mar 21.

Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

To determine whether the deletion of p16 can correct tooth and mandible growth retardation caused by Bmi1 deficiency, we compared the tooth and mandible phenotypes of homozygous p16-deficient (p16 ) mice, homozygous Bmi1-deficient (Bmi1 ) mice, double homozygous Bmi1 and p16-deficient (Bmi1 p16 ) mice to those of their wild-type littermates at 4 weeks of age by radiograph, histochemistry and immunohistochemistry. Results showed that compared to Bmi1 mice, the dental mineral density, dental volume and dentin sialoprotein immunopositive areas were increased, whereas the ratio of the predentin area to total dentin area and that of biglycan immunopositive area to dentin area were decreased in Bmi1 p16 mice. These results indicate that the deletion of p16 can improve tooth development in Bmi1 knockout mice. Compared to Bmi1 mice, the mandible mineral density, cortical thickness, alveolar bone volume, osteoblast number and activity, alkaline phosphatase positive area were all increased significantly in Bmi1 p16 mice. These results indicate that the deletion of p16 can improve mandible growth in Bmi1 knockout mice. Furthermore, the protein expression levels of cyclin D, CDK4 and p53 were increased significantly in p16 mice compared with those from wild-type mice; the protein expression levels of cyclin D and CDK4 were decreased significantly, whereas those of p27 and p53 were increased significantly in Bmi1 mice; these parameters were partly rescued in Bmi1 p16 mice compared with those from Bmi1 mice. Therefore, our results indicate that Bmi1 plays roles in regulating tooth and mandible development by inhibiting p16 signal pathway which initiated entry into cell cycle.
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http://dx.doi.org/10.1111/jcmm.16468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093977PMC
May 2021

Exogenous Coronavirus Interacts With Endogenous Retrotransposon in Human Cells.

Front Cell Infect Microbiol 2021 25;11:609160. Epub 2021 Feb 25.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.
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http://dx.doi.org/10.3389/fcimb.2021.609160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959850PMC
April 2021

Enhanced ascomycin production in Streptomyces hygroscopicus var. ascomyceticus by employing polyhydroxybutyrate as an intracellular carbon reservoir and optimizing carbon addition.

Microb Cell Fact 2021 Mar 17;20(1):70. Epub 2021 Mar 17.

Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China.

Background: Ascomycin is a multifunctional antibiotic produced by Streptomyces hygroscopicus var. ascomyceticus. As a secondary metabolite, the production of ascomycin is often limited by the shortage of precursors during the late fermentation phase. Polyhydroxybutyrate is an intracellular polymer accumulated by prokaryotic microorganisms. Developing polyhydroxybutyrate as an intracellular carbon reservoir for precursor synthesis is of great significance to improve the yield of ascomycin.

Results: The fermentation characteristics of the parent strain S. hygroscopicus var. ascomyceticus FS35 showed that the accumulation and decomposition of polyhydroxybutyrate was respectively correlated with cell growth and ascomycin production. The co-overexpression of the exogenous polyhydroxybutyrate synthesis gene phaC and native polyhydroxybutyrate decomposition gene fkbU increased both the biomass and ascomycin yield. Comparative transcriptional analysis showed that the storage of polyhydroxybutyrate during the exponential phase accelerated biosynthesis processes by stimulating the utilization of carbon sources, while the decomposition of polyhydroxybutyrate during the stationary phase increased the biosynthesis of ascomycin precursors by enhancing the metabolic flux through primary pathways. The comparative analysis of cofactor concentrations confirmed that the biosynthesis of polyhydroxybutyrate depended on the supply of NADH. At low sugar concentrations found in the late exponential phase, the optimization of carbon source addition further strengthened the polyhydroxybutyrate metabolism by increasing the total concentration of cofactors. Finally, in the fermentation medium with 22 g/L starch and 52 g/L dextrin, the ascomycin yield of the co-overexpression strain was increased to 626.30 mg/L, which was 2.11-fold higher than that of the parent strain in the initial medium (296.29 mg/L).

Conclusions: Here we report for the first time that polyhydroxybutyrate metabolism is beneficial for cell growth and ascomycin production by acting as an intracellular carbon reservoir, stored as polymers when carbon sources are abundant and depolymerized into monomers for the biosynthesis of precursors when carbon sources are insufficient. The successful application of polyhydroxybutyrate in increasing the output of ascomycin provides a new strategy for improving the yields of other secondary metabolites.
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http://dx.doi.org/10.1186/s12934-021-01561-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968196PMC
March 2021

Profiling of MicroRNAs Involved in Mepiquat Chloride-Mediated Inhibition of Internode Elongation in Cotton ( L.) Seedlings.

Front Plant Sci 2021 24;12:643213. Epub 2021 Feb 24.

College of Life Sciences, Henan Normal University, Xinxiang, China.

Mepiquat chloride (MC) is the most important plant growth retardant that is widely used in cotton ( L.) production to suppress excessive vegetative growth and improve plant architecture. MicroRNAs (miRNAs) are important gene expression regulators that control plant growth and development. However, miRNA-mediated post-transcriptional regulation in MC-induced growth inhibition remains unclear. In this study, the dynamic expression profiles of miRNAs responsive to MC in cotton internodes were investigated. A total of 508 known miRNAs belonging to 197 families and five novel miRNAs were identified. Among them, 104 miRNAs were differentially expressed at 48, 72, or 96 h post MC treatment compared with the control (0 h); majority of them were highly conserved miRNAs. The number of differentially expressed miRNAs increased with time after treatment. The expression of 14 known miRNAs was continuously suppressed, whereas 12 known miRNAs and one novel miRNA were continuously induced by MC. The expression patterns of the nine differentially expressed miRNAs were verified using qRT-PCR. The targets of the known and novel miRNAs were predicted. Four conserved and six novel targets were validated using the RLM-5' RACE assay. This study revealed that miRNAs play crucial regulatory roles in the MC-induced inhibition of internode elongation. It can improve our understanding of post-transcriptional gene regulation in MC-mediated growth inhibition and could potentially facilitate the breeding of dwarf cotton.
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http://dx.doi.org/10.3389/fpls.2021.643213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943613PMC
February 2021

Combining task-based rehabilitative training with PTEN inhibition promotes axon regeneration and upper extremity skilled motor function recovery after cervical spinal cord injury in adult mice.

Behav Brain Res 2021 May 20;405:113197. Epub 2021 Feb 20.

Department of Rehabilitation Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address:

Background: Conditional deletion of Pten in corticospinal neurons promotes axon sprouting and regeneration after spinal cord injury (SCI). However, regeneration studies targeted on PTEN inhibition seldom show motor function recovery. The promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism.

Purpose: To investigate the combined effects of PTEN inhibition and rehabilitative training on axon regeneration and subsequent motor functional improvement after cervical spinal cord injury.

Methods: Lentiviral particles (Lenti-PTEN-RNAi or Lenti-Scrambled-EGFP) were injected into the right sensorimotor mouse cortex in four experimental groups (PTEN RNAi + Training, PTEN RNAi, Control + Training, Control). Two weeks after injection, all mouse groups received a left C5 crush injury. We performed task-based rehabilitative training for 4 weeks on the PTEN RNAi + Training and Control + Training groups. Biotinylated dextran amine (BDA) was used for anterograde tracing of the dorsal corticospinal tract (dCST). We analysed axonal regeneration through immunohistochemical methods. A battery of behavioral tests was employed to assess functional recovery at Day3 and every other week after injury.

Results: Combining rehabilitative training with PTEN inhibition induced more axon regeneration and synapse reformation in the spinal cord caudal to the lesion site. Rostral to the lesion, the transected dCST axons sprouted into gray matter upon contact. Furthermore, forelimb function was found to be improved after combination therapy during behavioral testing.

Conclusion: Combining task-based rehabilitative training with PTEN inhibition further promotes axon regeneration, synaptic plasticity and reorganization of the neural network, with significant improvement in forelimb skilled motor function after cervical spinal cord injury. Our study provides new therapeutic insights for spinal cord injury management in the future.
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http://dx.doi.org/10.1016/j.bbr.2021.113197DOI Listing
May 2021

Doubly N-confused phlorin and phlorinone analogue.

Chem Commun (Camb) 2021 Mar;57(22):2772-2775

Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education & Hubei Key Laboratory of Catalysis and Materials Science, South-Central University for Nationalities, Wuhan 430074, China.

A doubly N-confused phlorin and phlorinone analogue were synthesized from a β,β'-linked dipyrromethane precursor and characterized by means of NMR and UV-Vis spectroscopies, X-ray crystallography, and electrochemistry. Solvents have a considerable impact on the optical absorption of the doubly N-confused phlorin so that it can differentiate simple alcohols such as methanol and ethanol.
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http://dx.doi.org/10.1039/d1cc00216cDOI Listing
March 2021
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