Publications by authors named "Yuanyuan Zhang"

1,792 Publications

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Emerging functions of circular RNA in the regulation of adipocyte metabolism and obesity.

Cell Death Discov 2022 May 20;8(1):268. Epub 2022 May 20.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, 225009, Yangzhou, Jiangsu, China.

As noncoding RNAs, circular RNAs (circRNAs) are covalently enclosed endogenous biomolecules in eukaryotes that have tissue specificity and cell specificity. circRNAs were once considered a rare splicing byproduct. With the development of high-throughput sequencing, it has been confirmed that they are expressed in thousands of mammalian genes. To date, only a few circRNA functions and regulatory mechanisms have been verified. Adipose is the main tissue for body energy storage and energy supply. Adipocyte metabolism is a physiological process involving a series of genes and affects biological activities in the body, such as energy metabolism, immunity, and signal transmission. When adipocyte formation is dysregulated, it will cause a series of diseases, such as atherosclerosis, obesity, fatty liver, and diabetes. In recent years, many noncoding RNAs involved in adipocyte metabolism have been revealed. This review provides a comprehensive overview of the basic structure and biosynthetic mechanism of circRNAs, and further discusses the circRNAs related to adipocyte formation in adipose tissue and liver. Our review will provide a reference for further elucidating the genetic regulation mechanism of circRNAs involved in adipocyte metabolism.
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http://dx.doi.org/10.1038/s41420-022-01062-wDOI Listing
May 2022

Bioinspired Metalation of the Metal-Organic Framework MIL-125-NH2 for NADH Regeneration and Gas-Liquid-Solid Three-Phase Enzymatic CO2 Reduction.

Angew Chem Int Ed Engl 2022 May 18. Epub 2022 May 18.

Qingdao University of Science and Technology, College of Materials Science and Engineering, No. 53 Zhengzhou Road, 266042, Qingdao, CHINA.

Coenzyme NADH regeneration is crucial for sustained photoenzymatic catalysis of CO2 reduction. However, light-driven NADH regeneration still suffers from the low regeneration efficiency and requires the combined use of homogeneous Rh complex. Herein, a Rh complex-based electron transfer unit was chemically attached onto the linker of MIL-125-NH2. The coupling between the light-harvesting iminopyridine unit and electron-transferring Rh-complex facilitated the photo-induced electron transfer for the NADH regeneration with the yield of 66.4% in 60 mins for 5 cycles. The formate dehydrogenase was further deposited onto the hydrophobic layer of the membrane by reverse filtering technique, which form the gas-liquid-solid reaction interface around the enzyme site, could demonstrate enhanced formic acid yield of 9.5 mM in 24 hours coupled with the in-situ regenerated NADH. The work could shed light on the construction of integrated inorganic-enzyme hybrid system for artificial photosynthesis.
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http://dx.doi.org/10.1002/anie.202206283DOI Listing
May 2022

Domestic physical activity and new-onset hypertension: A nationwide cohort study in China.

Am J Med 2022 May 15. Epub 2022 May 15.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory; Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou, China; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Institute of Biomedicine, Anhui Medical University, Hefei 230032, China. Electronic address:

Background: The association between domestic physical activity and the risk of hypertension remains uncertain. We aimed to evaluate the prospective relation of domestic physical activity and new-onset hypertension among Chinese males and females.

Methods: A total of 9254 adults who were free of hypertension at baseline were enrolled from the China Health and Nutrition Survey (CHNS). Data on domestic physical activity were obtained by using self-reported questionnaires, and calculated as metabolic equivalent task (MET)-hours/week. MET-hours/week may account for both intensity and time spent on activities. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg or diagnosed by physician or under antihypertensive treatment during the follow-up.

Results: During a median of 8.0 years (81,996 person-years) of follow-up, a total of 2892 participants developed hypertension. Overall, there were reversed J-shaped associations between the domestic physical activity and new-onset hypertension in both males and females (both P values for nonlinearity<0.001). Consistently, when domestic physical activity was assessed as categories (<10, 10-<20, 20-<30, 30-<40, 40-<50, 50-<60, 60-<70, 70-<80, 80-<90, 90-<100, ≥100 MET-hours/week), compared with those with domestic physical activity <10 MET-hours/week, the lower and similar risks of new-onset hypertension were found in participants with domestic physical activity 30-<90 MET-hours/week in both males and females.

Conclusion: Moderate domestic physical activity was associated with a lower risk of new-onset hypertension among both males and females.
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http://dx.doi.org/10.1016/j.amjmed.2022.04.023DOI Listing
May 2022

ACE2, BAT1, and SARS-CoV-2 spike protein: Structural and functional implications.

Curr Opin Struct Biol 2022 Apr 20;74:102388. Epub 2022 Apr 20.

Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China; Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China. Electronic address:

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a public health crisis and led to tremendous economic devastation. The spike protein (S) of SARS-CoV-2 hijacks the angiotensin converting enzyme 2 (ACE2) as a receptor for virus entry, representing the initial step of viral infection. S is one of the major targets for development of the antiviral drugs, antibodies, and vaccines. ACE2 is a peptidase that plays a physiologically important role in the renin-angiotensin system. Concurrently, it also forms dimer of heterodimer with the neutral amino acid transporter BAT1 to regulate intestinal amino acid metabolism. The symptoms of COVID-19 are closely correlated with the physiological functions of ACE2. In this review, we summarize the functional and structural studies on ACE2, BAT1, and their complex with S of SARS-CoV-2, providing insights into the various symptoms caused by viral infection and the development of therapeutic strategies.
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http://dx.doi.org/10.1016/j.sbi.2022.102388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108414PMC
April 2022

Nasal Caffeine Thermo-Sensitive in Situ Gel for Enhanced Cognition after Sleep-Deprivation.

Curr Drug Deliv 2022 May 9. Epub 2022 May 9.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China.

Background: Caffeine abundant in coffee has strong excitation effect on the central nerve system (CNS).

Methods: In order to combat the adverse effects of sleep deprivation on physical and mental health, this article designed a new nasal temperature-sensitive gel loaded with caffeine, whose effects of awakening and improving cognition in sleep-deprived rats were evaluated.

Results: It was found that the caffeine thermo-sensitive in situ gel (TSG) stayed in the nasal cavity for a longer time and increased the contact time between the drugs and the nasal mucosa, which made it possible for caffeine TSG to exert a lasting effect. Secondly, compared with sleep-deprived rats, those administrated with caffeine TSG were more responsive in behavioral experiments. Moreover, the anti-pentobarbital test proved that caffeine TSG could prolong the sleep latency and shorten the sleep time. Furthermore, caffeine TSG could significantly restore the cognitive ability by ameliorating neuronal cell injuries by upregulating brain-derived neurotrophic factor (BDNF) levels.

Conclusion: Generally, caffeine TSG could quickly exert the efficacy of enhancing cognition and wakefulness. and overcome the drawbacks of frequent medications. It can potentially be used for the treatment of psychiatric disorders, such as dementia, Parkinson and Alzheimer's disease.
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http://dx.doi.org/10.2174/1567201819666220509192200DOI Listing
May 2022

A Feasible Surface Patterning Method for SEM-DIC: Achieving High-Resolution Mapping of Local Strain and Microstructure to Reveal the Effect of Slip Transfer on Shear Strain Near Grain Boundaries.

Microsc Microanal 2022 May 16:1-14. Epub 2022 May 16.

School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001, P.R. China.

This paper exploited an alternative approach to prepare high-quality speckle patterns by uniformly dispersing nano-silica particles onto sample surfaces, helping digital image correlation (DIC) acquire the maximum spatial resolution of local strain up to 92 nm. A case study was carried out by combining this speckle pattern fabrication method with SEM-DIC and electron backscattering diffraction (EBSD). Thus, in situ mapping of local strain with ultra-high spatial resolution and microstructure in commercially pure titanium during plastic deformation could be achieved, which favored revealing the effect of slip transfer on shear strain near grain boundaries. Moreover, the slip systems could be easily identified via the combination of the SEM-DIC and EBSD techniques even though no obvious deformation trace was captured in secondary electron images. Additionally, the complex geometric compatibility factor $( {m}^{\prime}_c)$ relating to geometric compatibility factors (mʹ) and Schmid factors was proposed to predict the shear strain (εxy) at grain boundaries.
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http://dx.doi.org/10.1017/S1431927622000575DOI Listing
May 2022

Over-expression of EPB41L3 promotes apoptosis of human cervical carcinoma cells through PI3K/AKT signaling.

Acta Biochim Pol 2022 May 15. Epub 2022 May 15.

Fifth Department of Gynecologic Surgery, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, China.

Background: Cervical cancer is a significant malignancy of the female reproductive system. This study aimed to investigate the functions of Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) in cervical cancer and to explore its underlying mechanisms.

Methods And Results: Expression of EPB41L3 in cervical cancer was analyzed by in-depth mining in The Cancer Genome Atlas (TCGA) clinical sequencing database. Patients with high expression of EPB41L3 had a good prognosis. EPB41L3 was overexpressed in HeLa and SiHa cells by a chemically synthesized lentivirus; its overexpression significantly inhibited cell proliferation, promoted apoptosis of HeLa and SiHa cells, and suppressed tumorigenesis in nude mice bearing HeLa cells. The results of microarray analysis showed that EPB41L3 overexpression led to marked gene expression changes, including 258 up-regulated genes and 168 down-regulated genes. Furthermore, EPB41L3 overexpression inhibited PI3K and AKT phosphorylation, leading to the apoptosis of cervical cancer cells.

Conclusions: EPB41L3 overexpression inhibits cell proliferation, promotes apoptosis of cervical cancer cells, and suppresses tumorigenicity in vivo. Our findings suggest that EPB41L3 might be a new diagnostic biomarker and a therapeutic target for cervical cancer.
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http://dx.doi.org/10.18388/abp.2020_5649DOI Listing
May 2022

Microfluidic screening and genomic mutation identification for enhancing cellulase production in Pichia pastoris.

Biotechnol Biofuels Bioprod 2022 May 14;15(1):50. Epub 2022 May 14.

CAS Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.

Background: Pichia pastoris is a widely used host organism for heterologous production of industrial proteins, such as cellulases. Although great progress has been achieved in improving protein expression in P. pastoris, the potential of the P. pastoris expression system has not been fully explored due to unknown genomic impact factors. Recently, whole-cell directed evolution, employing iterative rounds of genome-wide diversity generation and high-throughput screening (HTS), has been considered to be a promising strategy in strain improvement at the genome level.

Results: In this study, whole-cell directed evolution of P. pastoris, employing atmospheric and room temperature plasma (ARTP) mutagenesis and droplet-based microfluidic HTS, was developed to improve heterogenous cellulase production. The droplet-based microfluidic platform based on a cellulase-catalyzed reaction of releasing fluorescence was established to be suitable for methanol-grown P. pastoris. The validation experiment showed a positive sorting efficiency of 94.4% at a sorting rate of 300 droplets per second. After five rounds of iterative ARTP mutagenesis and microfluidic screening, the best mutant strain was obtained and exhibited the cellulase activity of 11,110 ± 523 U/mL, an approximately twofold increase compared to the starting strain. Whole-genome resequencing analysis further uncovered three accumulated genomic alterations in coding region. The effects of point mutations and mutant genes on cellulase production were verified using reconstruction of point mutations and gene deletions. Intriguingly, the point mutation Rsc1 was observed in all the top-performing producers selected from each round, and gene deletion analysis confirmed that Rsc1, a component of the RSC chromatin remodeling complex, might play an important role in cellulase production.

Conclusions: We established a droplet-based microfluidic HTS system, thereby facilitating whole-cell directed evolution of P. pastoris for enhancing cellulase production, and meanwhile identified genomic alterations by whole-genome resequencing and genetic validation. Our approaches and findings would provide guides to accelerate whole-cell directed evolution of host strains and enzymes of high industrial interest.
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http://dx.doi.org/10.1186/s13068-022-02150-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107654PMC
May 2022

The Mediation Role of Health Behaviors in the Association between Self-Regulation and Weight Status among Preschool Children: A Sex-Specific Analysis.

Nutrients 2022 Apr 19;14(9). Epub 2022 Apr 19.

Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan 430030, China.

Previous studies have supported the link between children's self-regulation (CSR) and weight status, but the potential pathways have not been elucidated yet. We aimed to investigate whether and to what extent health behaviors mediate this association, as well as to explore the sex effect. For this study, we recruited 3740 preschoolers in Wuhan, China. The height and weight of children were measured, and a body mass index of the ≥85th percentile was defined as overweight/obesity (OWO). We used the Children's Behavior Questionnaire, with measured domains including inhibitory control, impulsivity, anger, and attentional focusing, to assess CSR. The primary caregivers' SR (PSR) was assessed with the Self-Control Scale. Information on lifestyles collected from questionnaires was utilized to construct the health behavior index (HBI). We found that Children's HBI was associated with both CSR and PSR, inhibitory control (OR = 0.81, < 0.001), anger (OR = 1.23, < 0.001), attentional focusing (OR = 0.70, < 0.001), impulsivity (OR = 1.23, < 0.001), and PSR (OR = 0.73, < 0.001). Children's impulsivity was associated with their OWO (OR = 1.11, = 0.013) which was partly mediated by the HBI (direct effect: β = 0.092, = 0.026; indirect effect: β = 0.011, = 0.007). The sex-specific analysis indicated that this mediation effect was only significant in boys. These results indicated that impulsivity is associated with childhood weight status, which is partially mediated by health behaviors, especially in boys.
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http://dx.doi.org/10.3390/nu14091692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104780PMC
April 2022

Assessment of chicken intestinal hydrolysates as a new protein source to replace fishmeal on the growth performance, antioxidant capacity and intestinal health of common carp (Cyprinus carpio).

Fish Shellfish Immunol 2022 May 11;125:161-170. Epub 2022 May 11.

Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin, 150070, China. Electronic address:

Promoting circular economy by transforming food residues into alternative high-value protein sources for aquaculture feed is a new way to develop alternative raw materials for fishmeal. This study systematically evaluated the effects of chicken intestinal hydrolysates (CIH) on the intestinal immune health of common carp through growth performance, antioxidant capacity, and intestinal immunity analysis in order to replace fishmeal. Five iso-nitrogenous and iso-lipidic experimental feeds were formulated to replace 0% (CIH-0), 25% (CIH-25), 50% (CIH-50), 75% (CIH-75) and 100% (CIH-100) of the fishmeal with CIH. Each experimental diet was fed to triplicate groups of 30 carp for 8 weeks. The results revealed that no significant differences in the final body weight, weight gain rate, feed coefficient radio, feed intake and protein efficiency ratio were found among the CIH-0, CIH-25, and CIH-50 groups, while the final body weight and weight gain rate in the CIH-75 and CIH-100 groups were significantly decreased and the feed coefficient radio was significantly increased. The aspartate aminotransferase of all CIH groups were significantly decrease, and the total protein, albumin did not differ among the CIH-0, CIH-25, CIH-50, and CIH-75 groups. The trypsin content was significantly increased in the CIH-75 and CIH-100 groups. No significant differences in the antioxidant index (catalase, glutathione peroxidase and malonaldehyde) were found among all CIH groups compared with the CIH-0 group. The expression levels of pro-inflammatory cytokines IL-1β and TNF-α were significantly down-regulated in the CIH-50 group and anti-inflammatory cytokines IL-10 and TGF-β2 were significantly up-regulated in the CIH-50 and CIH-75 groups. No significant differences in the expression levels of claudin-1, claudin-7 and claudin-11 were observed between the CIH-0 and CIH-50 groups, while the expression levels of ZO-1, occludin and MLCK were significantly up-regulated in the CIH-50 group compared with the CIH-0 group. The expression level of claudin-1 was down-regulated in the CIH-75 and CIH-100 groups. Hence, the study demonstrated the potential of CIH as a novel protein source for replacing fishmeal, and replacing 50% of fishmeal with CIH did not significantly influence the growth performance, immune responses, and intestinal barrier of common carp (Cyprinus carpio).
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http://dx.doi.org/10.1016/j.fsi.2022.05.011DOI Listing
May 2022

Terrigenous organic carbon drives methane dynamics in cascade reservoirs in the upper Yangtze China.

Water Res 2022 May 4;219:118546. Epub 2022 May 4.

College of River and Ocean Engineering, Chongqing Jiaotong University, Chongqing, 400074, China.

Methane (CH) emissions from freshwaters to the atmosphere have a profound impact on global atmospheric greenhouse gas (GHG) concentrations. Anthropogenic footprints such as dam construction and reservoir operation significantly changed the fate and transport of CH in freshwaters. The source of particulate organic carbon (POC) in reservoirs is a critical factor controlling CH production and emissions. However, little is known of how reservoir operation mediates the transport of POC and regulates CH accumulation in cascade hydroelectric reservoirs. Here, spatial and temporal variations in POC and CH were explored in the Xiluodu (XLD) and Xiangjiaba (XJB) reservoirs which are deep valley cascade reservoirs located in the main channel of the upper Yangtze River. Based on the δC-POC and N/C mole ratio of particulate organic matter, the results of multi-endmember stable isotope mixing models by a Bayesian model showed that terrigenous POC and autochthonous POC accounted for approximately 55% ± 18% and 43% ± 19% (SD, n = 179) of POC, respectively. Together with other hydrological and environmental parameters, we found that the input of terrigenous POC was dominantly influenced by water level variations and flow regulation due to reservoir operation. The cumulative effect of POC caused by cascade dams was not apparent. Terrigenous POC were more likely to drive CH accumulation in our study. Evident low level of CH in both reservoirs were likely affected by low sedimentation of POC and microbial CH oxidation. We hope our study could provide a conceptual framework for further modeling of CH dynamics in cascade reservoirs.
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http://dx.doi.org/10.1016/j.watres.2022.118546DOI Listing
May 2022

Pickering Emulsions Stabilized by Tea Water-Insoluble Protein Nanoparticles From Tea Residues: Responsiveness to Ionic Strength.

Front Nutr 2022 26;9:892845. Epub 2022 Apr 26.

College of Food Science, South China Agricultural University, Guangzhou, China.

Tea water-insoluble protein nanoparticles (TWIPNs) can be applied to stabilize Pickering emulsions. However, the effect of ionic strength (0-400 mmol/L) on the characteristics of Pickering emulsions stabilized by TWIPNs (TWIPNPEs) including volume-averaged particle size (d), zeta potential, microstructure and rheological properties is still unclear. Therefore, this work researched the effect of ionic strength on the characteristics of TWIPNPEs. The d of TWIPNPEs in the aquatic phase increased with the increase in ionic strength (0-400 mmol/L), which was higher than that in the SDS phase. Furthermore, the flocculation index of TWIPNPEs significantly ( < 0.05) increased from 24.48 to 152.92% with the increase in ionic strength. This could be verified from the microstructure observation. These results indicated that ionic strength could promote the flocculation of TWIPNPEs. Besides, the absolute values of zeta potential under different ionic strengths were above 40 mV in favor of the stabilization of TWIPNPEs. The viscosity of TWIPNPEs as a pseudoplastic fluid became thin when shear rate increased from 0.1 to 100 s. The viscoelasticity of TWIPNPEs increased with increasing ionic strength to make TWIPNPEs form a gel-like Pickering emulsion. the possible mechanism of flocculation stability of TWIPNPEs under different ionic strengths was propose. TWIPNs adsorbed to the oil-water interface would prompt flocculation between different emulsion droplets under the high ionic strength to form gel-like behavior verified by CLSM. These results on the characteristics of TWIPNPEs in a wide ionic strength range would provide the theoretical basis for applying Pickering emulsions stabilized by plant proteins in the food industry.
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http://dx.doi.org/10.3389/fnut.2022.892845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087344PMC
April 2022

Overexpression of MCAM induced by SMYD2-H3K36me2 in breast cancer stem cell properties.

Breast Cancer 2022 May 12. Epub 2022 May 12.

Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44, Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, People's Republic of China.

Background: Melanoma cell adhesion molecule (MCAM) is highly expressed in various malignancies. However, studies on the effects of MCAM on stemness of cancer stem cells are limited. Here, we aimed to explore the relationship between MCAM and stem cell phenotype in breast cancer (BC).

Methods: We analyzed the genes differentially expressed in BC from the oncomine database, followed by TCGA-BRCA database validation. We then used gene set enrichment analysis to analyze the signaling pathways enriched to the relevant genes, followed by loss-of-function experiments to analyze the role of MCAM in the growth of BC cells and the maintenance of stem cell properties. We analyzed the cause for the MCAM overexpression using ChIP-seq and clarified the upstream mechanism by constructing SE-Deleted cells. Finally, the role of SMYD2 in the growth of BC cells and the maintenance of stem cell properties were verified by rescue experiments.

Results: MCAM was significantly overexpressed in BC, which predicted somber prognosis in patients. Knockdown of MCAM drastically hindered the growth and metastasis of BC cells in vitro and in vivo. Subsequently, the MCAM promoter was observed to have significant H3K36me2 modification and that SMYD2 could significantly promote the expression of MCAM. In addition, further overexpression of SMYD2 in cells with MCAM knockdown increased MCAM expression and promoted the growth as well as stemness of BC cells.

Conclusion: SMYD2 can elevate the expression of MCAM by promoting its H3K36me2 modification, which in turn expedites the growth and stem cell properties of BC cells.
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http://dx.doi.org/10.1007/s12282-022-01365-xDOI Listing
May 2022

Generation of functional fat organoid from rat superficial fascia.

Adipocyte 2022 May 12. Epub 2022 May 12.

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, and Peking University Center for Obesity and Metabolic Disease Research, Beijing 100191, China.

The organoid is a 3D cell architecture formed by self-organized tissues or cells with similar cell types, histological structures, and biological functions of the native organ. Depending on the unique organ structures and cell types, the production of organoids requires individualized design and is still challenging. Organoids of some organs and tissues, including adipose tissue, remain to generate to be more faithful to their original organ in structure and function. We previously established a new model of the origin of adipose cells originating from non-adipose fascia tissue. Superficial fascia has abundant preadipocytes that are capable of adipogenic differentiation and are highly active . Here, we investigated superficial fascia fragments in 3D hydrogel and found they were able to transform into relatively large adipocyte aggregates containing mature unilocular adipocytes, which were virtually "fat organoids" of adipose tissue. Such fascia-originated fat organoids had a typical structure of adipose tissues and possessed the principal function of adipose cells in the synthesis, storage, hydrolysis of triglycerides and adipokines secretion. Producing fat organoids from superficial fascia can provide a new approach for adipocyte research and has broad applications in drug screening, plastic surgery, and regenerative medicine. Most importantly, the generation of fascia-derived functional fat organoids strongly evidences that both adipose tissues and cells originate from fascia. Our findings give insights into metabolic regulation by the crosstalk between multiple different organs and tissues and provide new knowledge for investigating novel treatments for obesity, diabetes and other metabolic diseases.
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http://dx.doi.org/10.1080/21623945.2022.2072446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116422PMC
May 2022

Mechanistic insights into CO pressure regulating microbial competition in a hydrogen-based membrane biofilm reactor for denitrification.

Chemosphere 2022 May 7;303(Pt 1):134875. Epub 2022 May 7.

State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.

CO is a proven pH regulator in hydrogen-based membrane biofilm reactor (H-MBfR) but how its pressure regulates microbial competition in this system remains unclear. This work evaluates the CO pressure dependent system performance, CO allocation, microbial structure and activity of CO source H-MBfR. The optimum system performance was reached at the CO pressure of 0.008 MPa, and this pressure enabled 0.18 g C/(m·d) of dissolved inorganic carbon (DIC) allocated to denitrifying bacteria (DNB) for carbon source anabolism and denitrification-related proton compensation, while inducing a bulk liquid pH (pH 7.4) in favor of DNB activity by remaining 0.21 g C/(m·d) of DIC as pH buffer. Increasing CO pressure from 0.008 to 0.016 MPa caused the markedly changed DNB composition, and the diminished DNB population was accompanied by the enrichment of sulfate-reducing bacteria (SRB). A high CO pressure of 0.016 MPa was estimated to induce the enhanced SRB activity and weakened DNB activity.
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http://dx.doi.org/10.1016/j.chemosphere.2022.134875DOI Listing
May 2022

The Impact of Lockdown, Patient Classification, and the Large-Scale Case Screening on the Spread of the Coronavirus Disease 2019 (COVID-19) in Hubei.

Biomed Res Int 2022 6;2022:8920117. Epub 2022 May 6.

School of Information and Mathematics, Yangtze University, Jingzhou 434023, China.

The coronavirus disease (COVID-19) which emerged in Wuhan, China, in December 2019, is widely controlled now in China. However, the global epidemic is still severe. To study and comment on Hubei's approaches for responding to the disease, the paper considered some factors such as suspected cases (part of them are influenza patients or common pneumonia patients, etc.), quarantine, patient classification (three types), clinically diagnosed cases, and lockdown of Wuhan and Hubei. After that, the paper established an model based on the surveillance data of Hubei published by the Hubei Health Commission from 10 January 2020 to 30 April 2020 and used the fminsearch optimization method to estimate the optimal parameters of the model. We obtained the basic reproduction number = 3.1571 from 10 to 22 January. was calculated as 2.0471 from 23 to 27 January. From 28 January to 30 April, = 1.5014. Through analysis, it is not hard to find that the patients without classification during the period of confirmed cases will result in the cumulative number of cases in Hubei to increase. In addition, regarding the lockdown measures implemented by Hubei during the epidemic, our simulations also show that if the lockdown time of either Hubei or Wuhan is advanced, it will effectively curb the spread of the epidemic. If the lockdown measures are not taken, the total cumulative number of cases will increase substantially. From the results of the study, it can be concluded that the lockdown, patient classification, and the large-scale case screening are essential to slow the spread of COVID-19, which can provide references for other countries or regions.
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http://dx.doi.org/10.1155/2022/8920117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077452PMC
May 2022

GAS5 represses endometrial cancer development via promoting anti-tumor function of tumor-associated macrophages.

Cancer Sci 2022 May 9. Epub 2022 May 9.

Department of Gynecology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.

The tumor-suppressor role of Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) have been proven in various types of cancer. However, the specific function of GAS5 in tumor-associated macrophages (TAMs) of endometrial cancer (EC) is elusive. qPCR results showed that GAS5 expression increased in EC tissues and primary TAMs from EC tumors. TAMs infiltration was significantly positively associated with the developmental stage of EC. Direct co-culture of GAS5-overexpressing TAMs and EC cells showed that GAS5 enhanced phagocytosis, antigen presentation, and activation of cytotoxic T cells, and repressed "Don't eat me" signals between TAMs and EC cells. Tumor formation in immunodeficient mice showed that GAS5-overexpressing macrophages could repress EC formation in vivo. GAS5 promoted M1 polarization by activating the miR-21-PTEN-AKT signaling pathway and directly repressing the nuclear accumulation and phosphorylation of oncogenic yes-associated protein 1 (YAP1) in TAMs. GAS5 inhibited the development of EC from both innate and adaptive immunity by transforming TAMs from a pro-tumor to an anti-tumor phenotype. These anti-tumor effects of GAS5 on TAMs were mediated by the activation of the miR-21-PTEN-AKT pathway and inhibition of YAP1.
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http://dx.doi.org/10.1111/cas.15390DOI Listing
May 2022

Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling.

Acta Pharm Sin B 2022 Mar 22;12(3):1198-1212. Epub 2021 Sep 22.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By and experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression and abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.
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http://dx.doi.org/10.1016/j.apsb.2021.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069402PMC
March 2022

Design and Implementation of Obstetric Central Monitoring System Based on Medical Image Segmentation Algorithm.

J Healthc Eng 2022 28;2022:3545831. Epub 2022 Apr 28.

Obstetrics and Gynecology of Wuchang Hospital, Wuhan, Hubei 430063, China.

At present, the incidence of emergencies in obstetric care environment is gradually increasing, and different obstetric wards often have a variety of situations. Therefore, it can provide great help in clinical medicine to give early warning and plan coping plans according to different situations. This paper studied an obstetrics central surveillance system based on a medical image segmentation algorithm. Images obtained by central obstetrics monitoring are segmented, magnified in detail, and image features are extracted, collated, and trained. The normal distribution rule is used to classify the features, which are included in the feature library of the obstetric central monitoring system. In the gray space of the medical image, the statistical distribution of gray features of the medical image is described by the mixture model of Rayleigh distribution and Gaussian distribution. In the gray space of the medical image, Taylor series expansion is used to describe the linear geometric structure of medicine. The eigenvalues of Hessian matrix are introduced to obtain high-order multiscale features of medicine. The multiscale feature energy function is introduced into Markov random energy objective function to realize medical image segmentation. Compared with other segmentation algorithms, the accuracy and sensitivity of the proposed algorithm are 87.98% and 86.58%, respectively, which can clearly segment small medical features.
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http://dx.doi.org/10.1155/2022/3545831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072048PMC
May 2022

Circulating Exosomal miR-181b-5p Promoted Cell Senescence and Inhibited Angiogenesis to Impair Diabetic Foot Ulcer via the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway.

Front Cardiovasc Med 2022 20;9:844047. Epub 2022 Apr 20.

Hebei Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Endothelial cell dysfunction is the main contributing factor of diabetic foot ulcer (DFU). Circulating exosomes have been found to play an important role in many processes, such as cell senescence and angiogenesis. However, the underlying roles and mechanism of circulating exosomes in the onset and progression of DFU remain unclear. In this study, we isolated exosomes from the plasma of patients with DFU (DFU-Exos) and non-diabetic foot wounds (NDF-Exos). DFU-Exos promoted cell senescence and inhibited tube formation in Human Umbilical Vein Endothelial Cells (HUVECs), unlike NDF-Exos. Several datasets suggest that miR-181b-5p expression might be enriched in exosomes from DFU; this was verified using quantitative real-time PCR (qRT-PCR). We also found that miR-181b-5p, which was taken up by HUVECs, promoted cell senescence and inhibited tube formation. Dual luciferase reporter assay, qRT-PCR, Western blotting, and immunofluorescence staining confirmed that miR-181b-5p could negatively regulate nuclear factor erythroid 2-related factor 2 (NRF2) expression by binding to its 3' UTR, thus further suppressing heme oxygenase-1 (HO-1) expression. In addition, NRF2 and HO-1 inhibitors could also rescue the effects of senescence and tube formation exerted by miR-181b-5p inhibitor. experiments showed that exosomes isolated from HUVECs which inhibited miR-181b-5p expression promoted angiogenesis to further restore the capacity of wound healing. In conclusion, this study indicated that circulating exosomal miR-181b-5p promoted cell senescence and inhibited angiogenesis to impair wound healing in DFU by regulating the NRF2/HO-1 pathway.
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http://dx.doi.org/10.3389/fcvm.2022.844047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067436PMC
April 2022

Inhibition of human ether-à-go-go-related gene K+ currents expressed in HEK293 cells by three gingerol components from ginger.

J Pharm Pharmacol 2022 May 3. Epub 2022 May 3.

Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.

Objectives: Gingerols are bioactive compounds derived from ginger, our experiment investigates the effects of 6-, 8- and 10-Gin on the human ether-à-go-go-related gene (hERG) K+ channels by using patch clamp technology.

Key Findings: hERG K+ currents were suppressed by 6-, 8- and 10-Gin in a concentration-dependent manner. The IC50 values of 6-, 8- and 10-Gin were 41.5, 16.1 and 86.5 μM for the hERG K+ currents, respectively. The maximum inhibitory effects caused by 6-, 8- and 10-Gin were 44.3% ± 2.0%, 88.6% ± 1.3% and 63.1% ± 1.1%, respectively, and the effects were almost completely reversible.

Conclusion: These findings suggest that 8-Gin is the most potent hERG K+ channel inhibitor among gingerol components and may offer a new approach for understanding and treating cancer.
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http://dx.doi.org/10.1093/jpp/rgac029DOI Listing
May 2022

Enhanced Cancer Starvation Therapy Enabled by an Autophagy Inhibitors-Encapsulated Biomimetic ZIF-8 Nanodrug: Disrupting and Harnessing Dual Pro-Survival Autophagic Responses.

ACS Appl Mater Interfaces 2022 May 4;14(19):21860-21871. Epub 2022 May 4.

The Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.

Autophagy is an important protective mechanism in maintaining or restoring cell homeostasis under physiological and pathological conditions. Nanoparticles (NPs) with certain components and morphologies can induce autophagic responses in cancer cells, providing a new perspective for establishing cancer therapy strategies. Herein, a novel nanodrug system, cell membranes-coated zeolitic imidazolate framework-8 (ZIF-8) NPs encapsulating chloroquine (CQ) and glucose oxidase (GOx) (defined as [email protected]), is designed to achieve an enhanced anticancer effect with the combination of starvation therapy and an autophagy regulation strategy. It is found that ZIF-8 as a nanocarrier can induce autophagy to promote survival of cancer cells via the upstream Zn-stimulated mitochondrial reactive oxygen species (ROS) so that the anticancer effect is directly achieved by inhibiting this pro-survival autophagy using CQ released from [email protected] under a tumor acidic microenvironment. Moreover, a cancer cell under starvation caused by GOx harnesses autophagy to maintain intracellular ATP levels and resist starvation therapy. The released CQ further inhibits the starvation-induced pro-survival autophagy and cuts off the protective pathway of cancer cells, enhancing the anticancer efficiency of GOx-based starvation therapy. Significantly, the cell membrane coating endows [email protected] with excellent in vivo homotypic targeting ability. Both in vitro and in vivo results have confirmed the enhanced anticancer effect achieved by [email protected] with a negligible side effect.
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http://dx.doi.org/10.1021/acsami.2c00552DOI Listing
May 2022

RING Zinc Finger Proteins in Plant Abiotic Stress Tolerance.

Front Plant Sci 2022 14;13:877011. Epub 2022 Apr 14.

Shandong Provincial Key Laboratory of Plant Stress Research, College of Life Science, Shandong Normal University, Jinan, China.

RING zinc finger proteins have a conserved RING domain, mainly function as E3 ubiquitin ligases, and play important roles in plant growth, development, and the responses to abiotic stresses such as drought, salt, temperature, reactive oxygen species, and harmful metals. RING zinc finger proteins act in abiotic stress responses mainly by modifying and degrading stress-related proteins. Here, we review the latest progress in research on RING zinc finger proteins, including their structural characteristics, classification, subcellular localization, and physiological functions, with an emphasis on abiotic stress tolerance. Under abiotic stress, RING zinc finger proteins on the plasma membrane may function as sensors or abscisic acid (ABA) receptors in abiotic stress signaling. Some RING zinc finger proteins accumulate in the nucleus may act like transcription factors to regulate the expression of downstream abiotic stress marker genes through direct or indirect ways. Most RING zinc finger proteins usually accumulate in the cytoplasm or nucleus and act as E3 ubiquitin ligases in the abiotic stress response through ABA, mitogen-activated protein kinase (MAPK), and ethylene signaling pathways. We also highlight areas where further research on RING zinc finger proteins in plants is needed.
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http://dx.doi.org/10.3389/fpls.2022.877011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047180PMC
April 2022

Intranasal hydrogel of armodafinil hydroxypropyl-β-cyclodextrin inclusion complex for the treatment of post-traumatic stress disorder.

Saudi Pharm J 2022 Mar 19;30(3):265-282. Epub 2022 Jan 19.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation and physicochemical property investigation, the AIC was formed by lyophilization of armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-β-CD) aqueous solution, in which the molar ratio of armodafinil and HP-β-CD was 1-1. The AIC encapsulation efficiency (EE) was (90.98 ± 3.72)% and loading efficiency (LE) was (13.95 ± 0.47)% and it increased the solubility of armodafinil in aqueous solution to 21 times. AIC hydrogel was prepared by adding AIC to methylcellulose (MC) hydrogels (3.33% w/v), and its higher drug release amount and slower release rate were testified by the in-vitro release assay and the rheological test. The mucosa irritation of AIC hydrogel was also evaluated. Healthy group, Model group, Sertraline group with 30 mg/kg sertraline gavage, AIC Hydrogel group with 20 mg/kg AIC hydrogel intranasal administration and AIC Aqueous Solution group with 20 mg/kg AIC aqueous solution gavage were set up for the treatment of mice with PTSD generated from foot shock method. Based on freezing response test in fear-conditioning box and open field test, compared with other groups, PTSD mice in AIC Hydrogel group showed significant improvement in behavioral parameters after 11 days of continuous drug administration and 5 days of drug withdrawal. After sacrifice, the plasma CORT level of PTSD mice in AIC Hydrogel group was elevated compared to Model group. Besides, the western blot (WB) of hippocampal brain-derived neurotrophic factor (BDNF) and amygdala dopamine transporter (DAT) immunohistochemistry sections indicated that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. The brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and distribution of armodafinil. In short, AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.
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http://dx.doi.org/10.1016/j.jsps.2022.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051980PMC
March 2022

Prediction Models for Conversion From Mild Cognitive Impairment to Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Front Aging Neurosci 2022 7;14:840386. Epub 2022 Apr 7.

Evidence-Based Nursing, School of Nursing, Lanzhou University, Lanzhou, China.

Background And Purpose: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment (MCI) is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD.

Methods: We systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of bias assessment.

Results: In total, 18 articles describing the prediction models for conversion from MCI to AD were identified. The dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. Models in 12 studies were developed using the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). C-index/area under the receiver operating characteristic curve (AUC) of development models were 0.67-0.98, and the validation models were 0.62-0.96. MRI, apolipoprotein E genotype 4 (APOE4), older age, Mini-Mental State Examination (MMSE) score, and Alzheimer's Disease Assessment Scale cognitive (ADAS-cog) score were the most common and strongest predictors included in the models.

Conclusion: In this systematic review, many prediction models have been developed and have good predictive performance, but the lack of external validation of models limited the extensive application in the general population. In clinical practice, it is recommended that medical professionals adopt a comprehensive forecasting method rather than a single predictive factor to screen patients with a high risk of MCI. Future research should pay attention to the improvement, calibration, and validation of existing models while considering new variables, new methods, and differences in risk profiles across populations.
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http://dx.doi.org/10.3389/fnagi.2022.840386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049273PMC
April 2022

Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy.

J Nanobiotechnology 2022 Apr 29;20(1):206. Epub 2022 Apr 29.

School of Basic Medical Sciences, Xi'an Key Laboratory of Immune Related Diseases, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed.

Results: For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (- 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis.

Conclusion: Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.
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http://dx.doi.org/10.1186/s12951-022-01421-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052603PMC
April 2022

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination.

Signal Transduct Target Ther 2022 Apr 27;7(1):139. Epub 2022 Apr 27.

Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, 100071, China.

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.
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http://dx.doi.org/10.1038/s41392-022-00987-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044386PMC
April 2022

miR-144 inhibits the IGF1R-ERK1/2 signaling pathway via NUDCD1 to suppress the proliferation and metastasis of colorectal cancer cells: a study based on bioinformatics and in vitro and in vivo verification.

J Cancer Res Clin Oncol 2022 Apr 27. Epub 2022 Apr 27.

GCP Center/Institute of Drug Clinical Trials, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Purpose: Colorectal cancer (CRC) is a severe health condition characterized by high mortalities. NudC domain containing 1 (NUDCD1) is abnormally upregulated in multiple tumors and is recognized as a cancer antigen. In CRC, NUDCD1 upregulation accelerates tumor progression by activating the IGF1R-ERK1/2 signaling pathway. Its specific regulatory mechanisms, however, remain unclear.

Methods: In the present study, we predicted the regulators of NUDCD1 and analyzed the expression profile of NUDCD1 in CRC tissues using the gene chip dataset. We also determined the regulation between miR-144, NUDCD1 and IGF1R-ERK1/2 signaling in vitro and in vivo. Then, the expression of miR-144 in CRC tissues was detected and its cell functions were verified in vitro.

Results: As predicted by bioinformatics, we found that NUDCD1 is a predicted target of miR-144 and confirmed that miR-144 directly binds to NUDCD1. In vitro and in vivo, miR-144 was determined to specifically regulate NUDCD1 expression and as such, can reduce the activity of the IGF1R-ERK1/2 signaling pathway. Moreover, miR-144 was significantly downregulated in CRC tissues; its levels were significantly negatively correlated with CRC primary range and lymph node metastasis. Cell function studies verified that miR-144 acts as a tumor suppressor, because it significantly inhibits the proliferation, metastasis, and invasion of CRC cells as well as inducing cell cycle arrest and apoptosis.

Conclusions: Our study demonstrates that miR-144 regulates IGF1R-ERK1/2 signaling via NUDCD1 to inhibit CRC cell proliferation and metastasis. The miR-144/NUDCD1/IGF1R-ERK1/2 signaling axis may be crucial in the progression of CRC.
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http://dx.doi.org/10.1007/s00432-022-03951-0DOI Listing
April 2022

Preparation of a bis-Schiff base immobilized mesoporous SBA-15 nanosensor for the fluorogenic sensing and adsorption of Cu.

Dalton Trans 2022 May 10;51(18):7210-7222. Epub 2022 May 10.

Jiangsu Xinhai Senior High School, Lianyungang, 222005, P. R. China.

An inorganic-organic chemosensing material (MS-NSP) was developed by anchoring the bis-Schiff base fluorophore onto the channel surface of a SBA-15 mesoporous silica surface with a quaternary ammonium linker. The mesostructure, morphology, and spectral features of MS-NSP were systematically described. The nanohybrid could be implemented as a multifunctional fluorescent nanosensor for Cu ions. A good linearity was observed over the concentration range from 0 to 4 mM, and the lower Cu detection limit by MS-NSP was found to be 0.19 μM. Additionally, the fluorescence response of MS-NSP was remarkably specific for Cu ions compared to other competitive ionic species. Moreover, the MS-NSP can also be utilized as an adsorbent for the effective elimination of Cu from an aqueous solution. The kinetic features of adsorption were well described by the pseudo-second-order model and the sorption isotherm was in agreement with the Langmuir model. The theoretical maximum adsorption amount of Cu ions was determined at 58.5 mg g. Finally, the interaction of MS-NSP and Cu was investigated using theoretical calculations. Overall, the material in the present study is useful for both the sensitive detection and effective extraction of Cu ions.
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http://dx.doi.org/10.1039/d2dt00933aDOI Listing
May 2022

An integrated strategy for the systematic chemical characterization of Salvianolate lyophilized injection using four scan modes based on the ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry.

J Pharm Biomed Anal 2022 Jun 14;215:114769. Epub 2022 Apr 14.

Second Affiliated hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, PR China. Electronic address:

Salvianolate lyophilized injection (SLI), a freeze-dried powder injection derived from aqueous extract of S. miltiorrhiza, is therapeutically used to treat the syndrome of blood stasis and collateral blockage during the recovery period after stroke. To date, it has remained a significant challenge to comprehensively characterize the compounds of SLI, particularly the minor components with potential bioactivities, in one sample injection analysis. Using an integrative four scan modes approach coupled with ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (UHPLC-QTRAP-MS/MS), we propose a novel, sensitive, and simple strategy for systematic and rapid profiling of the chemical components of SLI. First, an in-house database of constituents from the water-soluble extract of Danshen was created. Second, the fragmentation behaviors of the representative components in SLI were obtained using the untargeted scan mode enhanced MS (EMS)-information dependent acquisition (IDA)-enhanced product ion (EPI). The specific fragments acquired were then utilized to conduct precursor ion (Prec) and neutral loss (NL)-IDA-EPI scans. Following that, a sensitive predictive multiple reaction monitoring (pMRM)-IDA-EPI scan method with 454 transitions was developed based on the prominent fragment ions and plausible predictions. A total of 171 compounds were tentatively identified from SLI. Among them, 27 minor components have not been previously reported. This strategy allows most isomeric compounds at trace levels to be readily distinguished and annotated. Finally, 15 batches of 13 representative components in SLI selected by the qualitative results were accurately quantified. Salvianolic acid A (Sal A), Sal B, Sal D, lithospermic acid (LA), and rosmarinic acid (RA) were proved to be the predominant constituents. Sal B had the highest amount (195.08-350.46 μg·mg), followed by LA, Sal A, Sal D, and RA. Moreover, these 15 batches of samples showed good uniformity, and no abnormal batches existed. These results suggest that this novel strategy can accelerate the identification of undiscovered chemical components and serve as an alternative method for in-depth profiling of compounds in other traditional Chinese medicines (TCMs).
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http://dx.doi.org/10.1016/j.jpba.2022.114769DOI Listing
June 2022
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