Publications by authors named "Yue Zhang"

4,139 Publications

  • Page 1 of 1

Rational Design of Conducting Polymer-Derived Tubular Carbon Nanoreactors for Enhanced Enzyme-like Catalysis and Total Antioxidant Capacity Bioassay Application.

Anal Chem 2022 Aug 11. Epub 2022 Aug 11.

Alan G. MacDiarmid Institute, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.

The design of void-confined tubular nanostructures has aroused significant interest for catalytic applications because of their distinct microenvironment to modulate the reaction kinetics. Herein, we propose a facile wrapping-pyrolysis strategy to confine Fe nanoparticles (Fe NPs) inside N-doped carbon nanotubes ([email protected] NTs) derived from [email protected] (PPy) core-sheath nanofibers (NFs). The resultant [email protected] NTs can act as efficient enzyme mimics and exhibit a significantly higher peroxidase (POD)-like catalytic activity than unconfined Fe NPs and bare NC NTs. Kinetic experiments demonstrate that the optimized void structure benefits the affinity with the POD substrates and achieves excellent catalytic efficiency. The mechanism study reveals that the generation of OH from HO endows [email protected] NTs with excellent POD-like performance. Furthermore, we develop a total antioxidant capacity (TAC) sensing platform on account of this efficient POD-like system, expanding their applications in the field of food safety and human healthcare.
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http://dx.doi.org/10.1021/acs.analchem.2c02511DOI Listing
August 2022

HEG1 as a novel potential biomarker for the prognosis of lung adenocarcinoma.

Cancer Med 2022 Aug 10. Epub 2022 Aug 10.

Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao, China.

Background: Heart development protein with EGF-like domains 1 (HEG1), generally related to angiogenesis and embryonic development, was reported to participate in the occurrence and progression of some tumors recently. However, the role of HEG1 in lung adenocarcinoma (LUAD) is unclear.

Patients And Methods: To explore the effect of HEG1 on LUAD, GEPIA platform and UALCAN database, as well as Kaplan-Meier plotter were adopted to analyze the association of HEG1 with clinicopathological characteristics and survival outcomes for LUAD firstly. And then the HEG1 in LUAD tissues, blood and cell lines were detected by qRT-PCR, western blot, immunofluorescence, immunohistochemistry, and ELISA. Gene set enrichment analysis (GSEA) was conducted to identify pathways that might be affected by HEG1 in LUAD.

Results: In this study, HEG1 in lung tissues and cell lines of LUAD were significantly downregulated compared to benign pulmonary disease tissues and alveolar epithelial cells (p < 0.05). Moreover, compared with other groups, patients with advanced tumor stage had lower HEG1 mRNA expression levels (p = 0.025), which were negatively correlated with Ki67 index in tumor tissues (r = -0.427, p = 0.033). On the other hand, the LUAD patients with lower HEG1 had shorter overall survival (OS) (HR = 0.51, 95% CI: 0.40-0.65, p < 0.001) according to Kaplan-Meier plotter. In addition, HEG1 in serum of LUAD patients was negatively associated with CEA (r = -0.636, p < 0.001). GSEA showed that HEG1 was enriched in various metabolic-related pathways, including glucose metabolism, lipid metabolism, and nucleotide metabolism signaling.

Conclusions: HEG1 was downregulated in LUAD patients and associated with poor prognosis, which indicating HEG1 may serve as a potential biomarker for diagnosis and prognosis of LUAD.
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http://dx.doi.org/10.1002/cam4.5081DOI Listing
August 2022

Genetically Engineered Hematopoietic Stem Cells Deliver TGF-β Inhibitor to Enhance Bone Metastases Immunotherapy.

Adv Sci (Weinh) 2022 Aug 10:e2201451. Epub 2022 Aug 10.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, China.

Owing to the immune microenvironment of bones and low selectivity of the drug, patients with bone metastases often respond poorly to immunotherapy. In this study, programmed cell death protein 1 (PD1)-expressing hematopoietic stem cells (HSCs) are genetically engineered for bone-targeted delivery of the transforming growth factor beta (TGF-β) small-molecule inhibitor SB-505124 ([email protected]). Intriguingly, compared to anti-PD-L1 monoclonal antibodies, as "living drugs", HSCs-PD-1 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD-1 molecules. The SB released from HSCs-PD-1 competitively bound to TGF-β receptors on CD4 T cells and facilitate CD4 T cell differentiation to helper T (T )1 and T 2 cells, thereby reprogramming the local immunosuppressive milieu of the bone marrow. Additionally, HSCs-PD-1 can block programmed death-ligand 1 on tumor and myeloid cells, resulting in reinvigorated anti-tumor immunity of T cells. In conclusion, in the present study, an alternative cell engineering strategy is delineated for immune checkpoint blockade therapy, to target bone metastasis using HSCs as a platform, which shows great promise in the treatment of bone metastases.
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http://dx.doi.org/10.1002/advs.202201451DOI Listing
August 2022

KMT2C mutation in a Chinese man with primary multidrug-resistant metastatic adenocarcinoma of rete testis: a case report.

BMC Urol 2022 Aug 9;22(1):123. Epub 2022 Aug 9.

Department of Oncology, General Hospital of Western Theatre Command, No. 270, Tianhui Road, Rongdu Avenue, Jinniu District, Chengdu, 610000, Sichuan, People's Republic of China.

Background: Adenocarcinoma of the rete testis (AORT) is an extremely rare malignant tumor with poor prognosis and limited responsiveness to traditional chemotherapy. Few previous studies have focused on the molecular mechanisms underlying therapy resistance in AORT and further scrutiny is required to enable searches for targeted drugs to guide treatment selection.

Case Presentation: The current case concerns a 55-year-old man with AORT who presented with isolated bone metastasis at initial diagnosis and experienced rapid disease progression after multi-line platinum-based combination chemotherapy. Next-generation sequencing revealed a novel somatic lysine methyltransferase 2C (KMT2C) c.5605 T > C mutation in exon 36 with an abundance of 49.27%. The patient received antiangiogenic drug treatment for 2 months but this was discontinued due to unacceptable anorexia and nausea. He survived for 12 months after diagnosis.

Conclusion: A potential correlation between AORT primary multi-drug resistance and KMT2C mutations is implied. Further studies are needed to determine the efficacy of PARP1/2 inhibitors for tumors with KMT2C mutations.
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http://dx.doi.org/10.1186/s12894-022-01075-8DOI Listing
August 2022

Genome-wide identification and expression analysis of carotenoid cleavage oxygenase genes in Litchi (Litchi chinensis Sonn.).

BMC Plant Biol 2022 Aug 9;22(1):394. Epub 2022 Aug 9.

Engineering Research Center of Selecting and Breeding New Tropical Crops Varieties, Ministry of Education, Horticulture College, Hainan University, Hainan, 570311, Haikou, China.

Background: Carotenoid cleavage oxygenases (CCOs) include the carotenoid cleavage dioxygenase (CCD) and 9-cis-epoxycarotenoid (NCED), which can catalize carotenoid to form various apocarotenoids and their derivatives, has been found that play important role in the plant world. But little information of CCO gene family has been reported in litchi (Litchi chinensis Sonn.) till date.

Results: In this study, a total of 15 LcCCO genes in litchi were identified based on genome wide lever. Phylogeny analysis showed that LcCCO genes could be classified into six subfamilies (CCD1, CCD4, CCD7, CCD8, CCD-like, and NCED), which gene structure, domain and motifs exhibited similar distribution patterns in the same subfamilies. MiRNA target site prediction found that there were 32 miRNA target sites in 13 (86.7%) LcCCO genes. Cis-elements analysis showed that the largest groups of elements were light response related, following was plant hormones, stress and plant development related. Expression pattern analysis revealed that LcCCD4, LcNCED1, and LcNCED2 might be involving with peel coloration, LcCCDlike-b might be an important factor deciding fruit flavor, LcNCED2 and LcNCED3 might be related to flower control, LcNCED1 and LcNCED2 might function in fruitlet abscission, LcCCD4a1, LcCCD4a2, LcCCD1, LcCCD4, LcNCED1, and LcNCED2 might participate in postharvest storage of litchi.

Conclusion: Herein, Genome-wide analysis of the LcCCO genes was conducted in litchi to investigate their structure features and potential functions. These valuable and expectable information of LcCCO genes supplying in this study will offer further more possibility to promote quality improvement and breeding of litchi and further function investigation of this gene family in plant.
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http://dx.doi.org/10.1186/s12870-022-03772-wDOI Listing
August 2022

Dual specificity phosphatase 1 attenuates inflammation-induced cardiomyopathy by improving mitophagy and mitochondrial metabolism.

Mol Metab 2022 Aug 6:101567. Epub 2022 Aug 6.

Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:

Objectives: Dual specificity phosphatase 1 (DUSP1) is regarded as an anti-inflammatory factor in cardiovascular disorders. Mitophagy removes damaged mitochondria and thus promotes mitochondrial regeneration. We investigated whether DUSP1 could attenuate inflammation-induced cardiomyopathy by improving mitophagy.

Methods: Lipopolysaccharide was used to induce septic cardiomyopathy in wild-type (WT) and DUSP1 transgenic (DUSP1) mice.

Results: Echocardiography revealed that lipopolysaccharide impaired heart function by reducing the cardiac systolic and diastolic capacities of WT mice. Freshly isolated single cardiomyocytes from lipopolysaccharide-treated WT mice also exhibited reduced contractile/relaxation parameters. However, DUSP1 overexpression not only maintained the mechanical properties of cardiomyocytes, but also improved heart performance. Lipopolysaccharide upregulated myocardial inflammatory gene transcription and adhesive factor expression, which increased myocardial neutrophil accumulation and cardiomyocyte apoptosis in WT mice. DUSP1 overexpression inhibited the inflammatory response and therefore promoted cardiomyocyte survival. Lipopolysaccharide disrupted mitochondrial respiration and metabolism in WT cardiomyocytes, but DUSP1 overexpression restored mitochondrial metabolism, maintained the mitochondrial membrane potential and inhibited mitochondrial reactive oxygen species production, possibly by increasing FUN14 domain-containing 1 (FUNDC1)-dependent mitophagy. Silencing of FUNDC1 abolished the protective effects of DUSP1 overexpression on cardiomyocytes and their mitochondria following lipopolysaccharide treatment.

Conclusion: These results demonstrated that DUSP1 is a novel anti-inflammatory factor that protects against septic cardiomyopathy by improving FUNDC1-induced mitophagy.
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http://dx.doi.org/10.1016/j.molmet.2022.101567DOI Listing
August 2022

Lower class people suffered more (but perceived fewer risk disadvantages) during the COVID-19 pandemic.

Asian J Soc Psychol 2022 Jun 3. Epub 2022 Jun 3.

Department of Experimental and Applied Psychology, VU Amsterdam Institute for Brain and Behavior Amsterdam (IBBA) Amsterdam The Netherlands.

Does COVID-19 affect people of all classes equally? In the current research, we focus on the social issue of risk inequality during the early stages of the COVID-19 pandemic. Using a nationwide survey conducted in China ( = 1,137), we predicted and found that compared to higher-class individuals, lower-class participants reported a stronger decline in self-rated health as well as economic well-being due to the COVID-19 outbreak. At the same time, we examined participants' beliefs regarding the distribution of risks. The results demonstrated that although lower-class individuals were facing higher risks, they expressed lesser belief in such a risk inequality than their higher-class counterparts. This tendency was partly mediated by their stronger endorsement of system-justifying beliefs. The findings provide novel evidence of the misperception of risk inequality among the disadvantaged in the context of COVID-19. Implications for science and policy are discussed.
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http://dx.doi.org/10.1111/ajsp.12543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348012PMC
June 2022

The upregulation of stromal antigen 3 expression suppresses the phenotypic hallmarks of hepatocellular carcinoma through the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways.

BMC Gastroenterol 2022 Aug 8;22(1):378. Epub 2022 Aug 8.

Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu, 233030, Anhui, China.

Background: The stromal antigen 3 (STAG3) gene encodes an adhesion complex subunit that can regulate sister chromatid cohesion during cell division. Chromosome instability caused by STAG3 gene mutation may potentially promote tumor progression, but the effect of STAG3 on hepatocellular carcinoma (HCC) and the related molecular mechanism are not reported in the literature. The mechanism of the occurrence and development of HCC is not adequately understood. Therefore, the biological role of STAG3 in HCC remains to be studied, and whether STAG3 might be a sensitive therapeutic target in HCC remains to be determined.

Methods: The expression and clinical significance of STAG3 in HCC tissues and cell lines were determined by RT-qPCR and immunohistochemistry analyses. The biological functions of STAG3 in HCC were determined through in vitro and in vivo cell function tests. The molecular mechanism of STAG3 in HCC cells was then investigated by western blot assay.

Results: The mRNA expression of STAG3 was lower in most HCC cells than in normal cells. Subsequently, an immunohistochemical analysis of STAG3 was performed with 126 samples, and lower STAG3 expression was associated with worse overall survival in HCC patients. Moreover, cytofunctional tests revealed that the lentivirus-mediated overexpression of STAG3 in HCC cells inhibited cell proliferation, migration, and invasion; promoted apoptosis; induced G1/S phase arrest in vitro; and inhibited tumor growth in vivo. Furthermore, studies of the molecular mechanism suggested that the overexpression of STAG3 increased Smad3 expression and decreased CDK4, CDK6, cyclin D1, CXCR4 and RhoA expression.

Conclusion: STAG3 exhibits anticancer effects against HCC, and these effects involve the Smad3-CDK4/CDK6-cyclin D1 and CXCR4/RhoA pathways. STAG3 is a tumor-suppressor gene that may serve as a potential target for molecular therapy, which provides a new idea for the treatment of HCC.
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http://dx.doi.org/10.1186/s12876-022-02400-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361574PMC
August 2022

Growth, biofilm formation and atrazine degrading gene (trzN) expression of Arthrobacter sp. DNS10 cultured with montmorillonite, kaolinite and goethite.

Chemosphere 2022 Aug 5;307(Pt 2):135904. Epub 2022 Aug 5.

School of Resources &; Environment, Northeast Agricultural University, Harbin, 150030, PR China; Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130132, PR China. Electronic address:

The viable and degradation potential of the strains which adhered to soil minerals are essential for eliminating organic pollutants from soil. Herein, the interaction (growth, biofilm formation and survive) of Arthrobacter sp. DNS10, an atrazine degrading strain, with three kinds of typical soil minerals, such as montmorillonite, kaolinite and goethite, as well as the atrazine degradation gene (trzN) expression of the strain in the minerals system were studied. The results showed that montmorillonite had significant promotion effect on the growth of strain DNS10, followed by kaolinite, but goethite significantly inhibited the growth of strain DNS10. In contrast, goethite notably promoted the biofilm formation and there was less biofilm detected in montmorillonite containing system. The percentage of the survival bacteria in the biofilm that formed on montmorillonite, kaolinite and goethite was 53.8%, 40.8% and 28.2%. In addition, there were more reactive oxygen species (ROS) were detected in the cells that exposed to goethite than those of the cells exposed to kaolinite and montmorillonite. These results suggest that the electrostatic repulsion between kaolinite/montmorillonite and strain DNS10 prevents them from contacting each other and facilitates bacterial growth by allowing the strain to obtain more nutrients. Oppositely, the needle-like morphology of goethite might damage the strain DNS10 cell when they were combined by electrostatic attraction, and the goethite induced ROS also aggravate the cytotoxicity of goethite on strain DNS10. In addition, the relative transcription of trzN in the cells contacted with montmorillonite, kaolinite and goethite was 0.94-, 0.27- and 0.20- fold of the no mineral exposure treatment. Briefly, this research suggests that the minerals with different structure and/or physicochemical characteristics might cause various trend for the biofilm formation and degradation potential of the bacteria.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135904DOI Listing
August 2022

Characterization of Streptococcus pneumoniae Macrolide Resistance and Its Mechanism in Northeast China over a 20-Year Period.

Microbiol Spectr 2022 Aug 8:e0054622. Epub 2022 Aug 8.

Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China.

Due to the resistance of Streptococcus pneumoniae to β-lactams, macrolides, and tetracyclines, treatment alternatives have become increasingly limited worldwide. We aim to describe the characterization of erythromycin-resistant S. pneumoniae (ERSP) strains in northeastern China over a period of 20 years. A total of 1,240 ERSP strains were collected and classified into five groups based on the ages of the patients. Etest strips and Kirby-Bauer disk diffusion were performed for drug susceptibility testing. The capsule swelling test was used for capsule typing. The phenotype of drug resistance was detected by the erythromycin and clindamycin double-disk method. The , , , and genes were detected by PCR. Among the 1,240 ERSP strains, 510 were invasive isolates, and 730 were noninvasive isolates. The results of drug susceptibility testing showed that the rates of resistance to penicillin, amoxicillin, cefotaxime, ceftriaxone, meropenem, tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol varied among the different age groups. 19F, 19A, 23F, 14, and 6B were the serotypes that were commonly found among ERSP strains. Among all strains, 99.03% (1,228/1,240) exhibited an MLSB (macrolide-lincosamide-streptogramin B) resistance phenotype, of which 1,221 strains displayed a constitutive MLSB (cMLSB) phenotype and 7 strains showed an inducible MLSB (iMLSB) phenotype. All of these strains carried the gene. In contrast, only 0.97% of strains of M phenotypes were found to carry the gene. Both the and genes were detected in 704 strains that exhibited multidrug resistance, whereas the gene was not detected. Furthermore, 1,185 tetracycline-resistant strains were found to carry the gene. Macrolide antimicrobial drugs should be used cautiously for the empirical treatment of S. pneumoniae infections. This study presents a retrospective analysis using 1,240 clinical erythromycin-resistant Streptococcus pneumoniae (ERSP) isolates collected in northeastern China between January 2000 and December 2019. The serotype distribution, corresponding vaccine coverage, as well as resistance phenotypes, genes, and mechanisms to macrolide and tetracycline of these isolates were systematically described, analyzed, and discussed. We hope that this study will inform clinicians in their respective regions when selecting antimicrobial agents. We also hope that this study is useful for researchers in related fields. Finally, we emphasize in this study that vaccination is the best preventive measure for S. pneumoniae infection considering its resistance to commonly used antibiotics. The determination of the S. pneumoniae serotype distribution also provides valuable empirical evidence for local health authorities when introducing appropriate vaccines in a specific area.
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http://dx.doi.org/10.1128/spectrum.00546-22DOI Listing
August 2022

Alteration of Manure Antibiotic Resistance Genes via Soil Fauna Is Associated with the Intestinal Microbiome.

mSystems 2022 Aug 8:e0052922. Epub 2022 Aug 8.

School of Geographical Sciences, Fujian Normal Universitygrid.411503.2, Fuzhou, China.

Livestock wastes contain high levels of antibiotic resistance genes (ARGs) and a variety of human-related pathogens. Bioconversion of livestock manure using larvae of the beetle Protaetia brevitarsis is an effective technique for waste reduction and value creation; however, the fate of manure ARGs during gut passage and interaction with the gut microbiome of remains unclear. To investigate this, we fed with dry chicken manure for 6 days and measured bacterial community dynamics and ARG abundance and diversity along the gut tract using high-throughput quantitative PCR and metagenomics approaches. The diversity of ARGs was significantly lower in larval midgut, hindgut, and frass than in raw chicken manure, and around 80% of pathogenicity-related genes (PRGs) exhibited reduced abundance. Network analysis demonstrated that and were the key bacterial phyla associated with ARG reduction. Metagenomic analysis further indicated that ARGs, mobile genetic elements (MGEs), and PRGs were simultaneously attenuated in the hindgut, implicating a decreased likelihood for horizontal gene transfer (HGT) of ARGs among bacteria and pathogens during manure bioconversion. Our findings demonstrated that the attenuation of ARGs is strongly associated with the variation of the gut microbiome of , providing insights into mechanisms of risk mitigation of ARG dissemination during manure bioconversion. Saprophagous fauna like the oriental edible beetle () plays a fundamental role in converting organic wastes into biofertilizer. Accumulating evidence has shown that soil fauna can reduce the abundance of ARGs, although the underlying mechanism of ARG reduction is still unclear. In our previous research, we found a large reduction of ARGs in vegetable roots and leaves from frass compared with raw manure, providing a promising biofertilizer for soil-vegetable systems. Therefore, in this study, temporal dynamic changes in the microbiomes of the donor (chicken manure) and host () were investigated, and we found a close association between the gut microbiome and the alteration of ARGs. These results shed new light on how the insect gut microbiome can mitigate manure-borne ARGs and provide insights into the bioconversion process via a typical member of the saprophagous fauna, .
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http://dx.doi.org/10.1128/msystems.00529-22DOI Listing
August 2022

Network pharmacology approach to investigate the multitarget mechanisms of Zhishi Rhubarb Soup on acute cerebral infarction.

Pharm Biol 2022 Dec;60(1):1394-1406

Nanjing Chinese Medicine Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing City, People's Republic of China.

Context: Zhishi Rhubarb Soup (ZRS) is a traditional Chinese medicine formula used in the clinic to treat acute cerebral infarction (ACI) for many years. However, the exact mechanism of the treatment remains unclear.

Objective: This study elucidates the multitarget mechanisms underlying the effects of ZRS on ACI using network pharmacology analysis and verify its effect by performing animal experiments.

Materials And Methods: Using the network pharmacology approach, the multiple components, critical targets and potential mechanisms of ZRS against ACI were investigated. Six herbal names of ZRS and 'acute cerebral infarction' were used as keywords to search the relevant databases. In addition, we established the MCAO model to verify the results of network pharmacology enrichment analysis. ZRS (10 g crude drug/kg) was gavaged once per day for 7 consecutive days beginning 3 h after model establishment. After ZRS treatment, TTC staining, Western blot analysis, IHC and ELISA were conducted to further explore the mechanism of ZRS intervention in ACI.

Results: The network pharmacology approach identified 69 key targets, 10 core genes and 169 signalling pathways involved in the treatment of ACI with ZRS. experiment showed that ZRS treatment significantly reduced cerebral infarction volume (42.76%). It also reduced the expression level of AGE, RAGE and P65; and inhibited the expression of inflammatory MMP-9 and IFN-γ.

Conclusions: This study demonstrated that ZRS improved cerebral ischaemic injury by inhibiting neuroinflammation partly via the AGE-RAGE signalling pathway. It provides a theoretical basis for the clinical application of ZRS in the treatment of ACI.
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http://dx.doi.org/10.1080/13880209.2022.2103718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364736PMC
December 2022

A decrease in physiological arousal accompanied by stable behavioral performance reflects task habituation.

Front Neurosci 2022 22;16:876807. Epub 2022 Jul 22.

Department of Behavioral Sciences and Learning, Linnaeus Centre HEAD, Swedish Institute for Disability Research, Linköping University, Linköping, Sweden.

Despite the evidence of a positive relationship between task demands and listening effort, the Framework for Understanding Effortful Listening (FUEL) highlights the important role of arousal on an individual's choice to engage in challenging listening tasks. Previous studies have interpreted physiological responses in conjunction with behavioral responses as markers of task engagement. The aim of the current study was to investigate the effect of potential changes in physiological arousal, indexed by the pupil baseline, on task engagement over the course of an auditory recall test. Furthermore, the aim was to investigate whether working memory (WM) capacity and the signal-to-noise ratio (SNR) at which the test was conducted had an effect on changes in arousal. Twenty-one adult hearing aid users with mild to moderately severe symmetrical sensorineural hearing loss were included. The pupil baseline was measured during the Sentence-final Word Identification and Recall (SWIR) test, which was administered in a background noise composed of sixteen talkers. The Reading Span (RS) test was used as a measure of WM capacity. The findings showed that the pupil baseline decreased over the course of the SWIR test. However, recall performance remained stable, indicating that the participants maintained the necessary engagement level required to perform the task. These findings were interpreted as a decline in arousal as a result of task habituation. There was no effect of WM capacity or individual SNR level on the change in pupil baseline over time. A significant interaction was found between WM capacity and SNR level on the overall mean pupil baseline. Individuals with higher WM capacity exhibited an overall larger mean pupil baseline at low SNR levels compared to individuals with poorer WM capacity. This may be related to the ability of individuals with higher WM capacity to perform better than individual with poorer WM capacity in challenging listening conditions.
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http://dx.doi.org/10.3389/fnins.2022.876807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355477PMC
July 2022

Active components and molecular mechanism of Lindl. in the treatment of endometritis based on pharmacology network prediction.

Front Vet Sci 2022 22;9:885952. Epub 2022 Jul 22.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Antibiotic treatment of endometritis was limited by the inevitable antibiotic residues and risk of bacterial resistance. Therefore, the development of safe and effective strategies for endometritis treatment is urgently needed. Lindl. (SOL) showed great pharmacological potential against endometritis. However, the active components and underlying mechanism of SOL for endometritis treatment remain indeterminate. In our study, the active components and possible molecular mechanism of SOL against endometritis were predicted through computer data mining and biological networks construction. It was predicted that the main active components of SOL were luteolin, kaempferol, oleanolic acid, and rutin, and their anti-endometritis effect was mainly attributed to the TLRs/NF-κB signaling pathway. Furthermore, a green and efficient deep eutectic solvent combined with ultrasound-assisted extraction (DES-UAE) was performed and optimized to obtain high contents of total flavonoid, rutin, and luteolin. The four predicted active components in the SOL extracts were qualitatively and quantitatively analyzed by LC/MS and HPLC. Finally, the pharmacological effects of SOL and active components have been verified by -endometritis models in mice. H&E staining and bacterial load in uterus tissues assays initially validated the pharmacodynamic effects of SOL, and quantitative real-time PCR (RT-qPCR) and ELISA results confirmed that SOL and four active components could ameliorate the uterus injury caused by , the mechanism of action is related to the TLRs/NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fvets.2022.885952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355479PMC
July 2022

Analysis of the OX40/OX40L immunoregulatory axis combined with alternative immune checkpoint molecules in pancreatic ductal adenocarcinoma.

Front Immunol 2022 22;13:942154. Epub 2022 Jul 22.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Immune checkpoint modulation has been a vital therapeutic option in many malignancies, and targeting of novel immune checkpoints, including OX40/OX40L costimulatory signaling, is being assessed in clinical trials. However, little is known about the role of OX40 and OX40L in pancreatic ductal adenocarcinoma (PDAC). Thus, we investigated the clinical significance of OX-40 and OX40L and their associations with alternative immune checkpoints, immune infiltrates, clinicopathological features, and clinical outcomes. We performed multiplexed immunofluorescence staining for OX40, OX40L, CD8, and CD68 using tissue microarrays from 255 patients. Immunohistochemistry data for PD-L1, B7-H3, B7-H4, CD3, and Foxp3 were analyzed. And the RNA sequencing data of OX40/OX40L in The Cancer Genome Atlas and International Cancer Genome Consortium databases were also evaluated. The positive rates for OX40 on tumor cells (TCs) and immune cells (ICs) were 8.6% and 10.2%, respectively, and the positive rates for OX40L on TCs, ICs, and macrophages were 20%, 40.4%, and 12.9%, respectively. OX40 was associated with favorable clinicopathological features. OX40+ on ICs, OX40L+ on TCs, or OX40L+ on macrophages, rather than the total gene and protein levels of OX40/OX40L, were associated with improved survival. OX40+ on ICs and OX40L+ on macrophages were independent factors of clinical outcomes. Moreover, we could more accurately stratify patients through the combination of OX40 on ICs and OX40L on TCs, and patients with OX40+ ICs and OX40L+CK+ showed the best outcome. And we demonstrated that patients with OX40-ICs and low CD8+ T cells infiltration had unfavorable survival. Intriguingly, OX40+ ICs or OX40L+ macrophages demonstrated superior survival in patients with PD-L1 negativity than in those with PD-L1 positivity. Furthermore, OX40+ ICs were correlated with negative B7-H4 on TCs, high densities of CD3 T cells, and high densities of Foxp3 T cells; OX40+ TCs and OX40L+ TCs were associated with low densities of Foxp3 T cells. We identified OX40 and OX40L as promising predictors for prognosis in PDAC.
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http://dx.doi.org/10.3389/fimmu.2022.942154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352865PMC
August 2022

DNA nanomachine activation and Zn imaging in living cells with single NIR irradiation.

Anal Chim Acta 2022 Aug 7;1221:340149. Epub 2022 Jul 7.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China. Electronic address:

Though activatable DNA nanomachines in response to external and internal stimuli successfully improve the temporal and spatial controllability of biosensing and bioimaging, current strategies usually apply different irradiation lights for DNA nanomachine activation and imaging processes. The involvement of short wavelength excitation results in shallow tissue penetration and high background interference. Here we design a photo-locked DNA nanomachine (P-DNA nanomachine) that uses single NIR irradiation for spatiotemporally activating nanomachine operation and metal ion imaging in cancer cells. Upconversion nanoparticles (UCNPs) are modified with energy collector dye FITC, photo-locked DNAzyme and its substrate strands labelled with BHQ1. Part of the UCNPs emission at 450 nm was collected by FITC and quenched by BHQ1 originally. 980 nm irradiation photolyzes PC linker, activates DNAzyme catalytic reaction in the presence of Zn, and recovers FITC luminance at 540 nm. The intracellular Zn amount was imaged by quantitatively measuring FITC recovery intensity versus internal standard of UCNPs luminance at 450 nm. The presented NIR activatable P-DNA nanomachine demonstrates effective protection against "false positive" signal from extracellular interference, thus has potential application for in vivo imaging.
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http://dx.doi.org/10.1016/j.aca.2022.340149DOI Listing
August 2022

Insights into the activity of nickel boride/nickel heterostructures for efficient methanol electrooxidation.

Nat Commun 2022 Aug 6;13(1):4602. Epub 2022 Aug 6.

Key Laboratory for Ultrafine Materials of Ministry of Education, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Designing efficient catalysts and understanding the underlying mechanisms for anodic nucleophile electrooxidation are central to the advancement of electrochemically-driven technologies. Here, a heterostructure of nickel boride/nickel catalyst is developed to enable methanol electrooxidation into formate with a Faradaic efficiency of nearly 100%. Operando electrochemical impedance spectroscopy and in situ Raman spectroscopy are applied to understand the influence of methanol concentration in the methanol oxidation reaction. High concentrations of methanol inhibit the phase transition of the electrocatalyst to high-valent electro-oxidation products, and electrophilic oxygen species (O* or OH*) formed on the electrocatalyst are considered to be the catalytically active species. Additional mechanistic investigation with density functional theory calculations reveals that the potential-determining step, the formation of *CHO, occurs most favorably on the nickel boride/nickel heterostructure rather than on nickel boride and nickel. These results are highly instructive for the study of other nucleophile-based approaches to electrooxidation reactions and organic electrosynthesis.
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http://dx.doi.org/10.1038/s41467-022-32443-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357015PMC
August 2022

Correlation between pleth variability index and ultrasonic inferior vena cava-collapsibility index in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia.

Eur J Med Res 2022 Aug 6;27(1):139. Epub 2022 Aug 6.

Department of Anesthesiology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, No. 123 Tianfei Xiang, Mochou Road, Nanjing, Jiangsu, 210004, People's Republic of China.

Background: To explore the correlation and consistency of non-invasive pleth variability index (PVI) combined with ultrasonic measurement of inferior vena cava-collapsibility index (IVC-CI) in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia.

Methods: Forty-seven twin pregnancies women undergoing elective cesarean section were selected. The ASA score was rated as I-II, aged from 18 to 45 years. Spinal anesthesia was performed at L3-4. PVI and IVC-CI, general data (BMI, gestational weeks, operation duration, blood loss), MAP, temperature sensory block level and adverse reactions were recorded at baseline (T1) and completion of testing the level of spinal anesthesia (T2).

Results: The correlation coefficient analysis of baseline IVC-CI% and PVI revealed that the Pearson's coefficient was 0.927, > 0.4. Thus, pre-anesthesia IVC-CI% had a strong correlation with PVI, with R of 85.69%. The correlation coefficient analysis of post-anesthesia IVC-CI% and PVI revealed that the Pearson's coefficient was 0.904, > 0.4. Thus, post-anesthesia IVC-CI% had a strong correlation with PVI, with R of 81.26%.

Conclusion: PVI is strongly consistent with ultrasound measurement of IVC-CI twin pregnancies, which can be used as a valuable index for predicting the volume in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. Trial registration This study was registered on ClinicalTrials.gov with clinical trial registration number of ChiCTR2200055364 (08/01/2022).
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http://dx.doi.org/10.1186/s40001-022-00771-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356457PMC
August 2022

Ginseng under forest exerts stronger anti-aging effects compared to garden ginseng probably via regulating PI3K/AKT/mTOR pathway, SIRT1/NF-κB pathway and intestinal flora.

Phytomedicine 2022 Jul 27;105:154365. Epub 2022 Jul 27.

College of Resources and Environment Sciences, Jilin Agricultural University, Changchun, China. Electronic address:

Background: Ginseng is deemed to be an effective anti-aging therapy. Evidence for differences in representative active ingredients and anti-aging effects between garden ginseng (GG) and ginseng under forest (FG) is insufficient.

Purpose: The study was designed to systematically analyze the differences in the mechanistic protective effects of GG and FG on aging mice based on their compositional differences.

Methods: The chemical ingredients in GG and FG were first determined. In vivo, D-galactose-induced aging mice were orally administered GG or FG (400 mg/kg/day) for 6 weeks. Behavioral parameters of mice were measured by the radial 8-arm maze, and the changes in body weight and organ indices were recorded. Blood, brain tissue, and feces were collected for biochemical analysis, histopathological staining, Western blotting, and 16S rDNA intestinal flora sequencing, respectively.

Results: The absolute contents of total ginsenosides, polyphenols, crude polysaccharides, starch, and protein in GG were 0.71, 0.68, 1.15, 2.27, and 1.08 folds higher than those in FG, respectively; while FG exhibited a higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) but lower relative content of starch than GG. GG and FG improved hippocampal lesions and poor weight gain, organ indices, and behavioral indices, and prevented excessive oxidative stress and acetylcholinesterase activity in aging mice. What's more, GG and FG treatment ameliorated excessive apoptosis and inflammatory reaction in the aging brain by modulating apoptosis-related proteins, PI3K/AKT/mTOR pathway, and SIRT1/NF-κB pathway. GG and FG also restored the diversity and structure of gut microbiota, up-regulated the relative abundance of beneficial bacteria (e.g., Lactobacillus), and tended to exert key anti-aging effects via the microbiota-gut-brain axis. Notably, in vivo experiments confirmed that FG had a stronger anti-aging activity than GG.

Conclusion: FG exerts a more powerful anti-aging effect than GG by regulating oxidative stress, apoptosis, inflammation, and the microbe-gut-brain axis, possibly relying on the higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) in FG.
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http://dx.doi.org/10.1016/j.phymed.2022.154365DOI Listing
July 2022

Silk protein/polyvinylpyrrolidone nanofiber membranes loaded with puerarin accelerate wound healing in mice by reducing the inflammatory response.

Biomater Adv 2022 Apr 22;135:212734. Epub 2022 Apr 22.

College of traditional Chinese Medicine, Jilin Agriculture Science and Technology College, Jilin 132101, China. Electronic address:

In modern clinical applications, wound healing remains a considerable challenge. Excessive inflammatory response is associated with delayed wound healing. In this study, we prepared composite nanofibrous membranes by mixing the Chinese herbal extract puerarin (PUE) with natural silk protein (SF) and synthetic polymer polyvinylpyrrolidone (PVP) using electrostatic spinning technique, and conducted a series of studies on the structural and biological properties of the fibrous membranes. The results showed that the loading of PUE increased the diameter, porosity and hydrophilicity of nanofibers, which were more favorable for cell adhesion and proliferation. ABTS radical scavenging assay also showed that the loading of PUE enhanced the antioxidant properties of the fibrous membranes. In addition, SF/PVP/PUE nanofibers are non-toxic and can be used as wound dressings. In vitro experiments showed that SF/PVP/PUE nanofibers could effectively alleviate lipopolysaccharide (LPS)-induced inflammation in Immortalized human keratinocytes (HaCaT) cells and down-regulate pro-inflammatory cytokine expression in cells. In vivo studies further showed that the SF/PVP/PUE nanofibers could effectively accelerate wound repair. The mechanism is that SF/PVP/PUE nanofibers can inhibit the activation and transduction of toll-like receptor 4/myeloid differentiation factor88/nuclear factor kappa B (TLR4/MyD88/NF-κB) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways, thereby reducing the inflammatory response and achieving wound healing.
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http://dx.doi.org/10.1016/j.bioadv.2022.212734DOI Listing
April 2022

Clinical practice guidelines and expert consensus statements on rehabilitation for patients with COVID-19: protocol for a systematic review.

BMJ Open 2022 08 4;12(8):e060767. Epub 2022 Aug 4.

School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China

Introduction: COVID-19 is a highly infectious disease, characterised by respiratory, physical and psychological dysfunctions. Rehabilitation could effectively alleviate the symptoms and promote recovery of the physical and mental health of patients with COVID-19. Recently, rehabilitation medical institutions have issued clinical practice guidelines (CPGs) and expert consensus statements involving recommendations for rehabilitation assessments and rehabilitation therapies for COVID-19. This systematic review aims to assess the methodological quality and reporting quality of the guidance documents, evaluate the heterogeneity of the recommendations and summarise the recommendations with respect to rehabilitation assessments and rehabilitation therapies for COVID-19 to provide a quick reference for front-line clinicians, therapists and patients as well as reasonable suggestions for future guidelines.

Methods And Analysis: The electronic databases including PubMed, Embase, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Wanfang Database and China National Knowledge Infrastructure (CNKI) and websites of governments or organisations (eg, National Guideline Clearinghouse, Guidelines International Network, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network and WHO) will be searched for eligible CPGs and expert consensus statements from inception to August 2022. CPGs and expert consensus statements published in Chinese or English and presenting recommendations for modern functional rehabilitation techniques and/or traditional Chinese medicine rehabilitation techniques for COVID-19 will be included. Reviews, interpretations, old versions of CPGs and expert consensus statements and those for the management of other diseases during the pandemic will be excluded. Two reviewers will independently review each article, extract data, appraise the methodological quality following the Appraisal of Guidelines for Research & Evaluation II tool and assess the reporting quality with the Reporting Items for Practice Guidelines in Healthcare statement. The Measurement Scale of Rate of Agreement will be used to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements. Agreement between reviewers will be calculated using the intraclass correlation coefficient. We will also summarise the recommendations for rehabilitation in patients with COVID-19. The results will be narratively described and presented as tables or figures.

Ethics And Dissemination: Ethics approval is not needed for this systematic review because information from published documents will be used. The findings will be submitted for publication in a peer-reviewed journal and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Prospero Registration Number: CRD42020190761.
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http://dx.doi.org/10.1136/bmjopen-2022-060767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358617PMC
August 2022

Rapid screening of hepatotoxic components in Uncariae Ramulus Cum Uncis based on "component-target-pathway" network.

J Pharm Biomed Anal 2022 Jul 26;219:114968. Epub 2022 Jul 26.

Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin 301617, China. Electronic address:

As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.
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http://dx.doi.org/10.1016/j.jpba.2022.114968DOI Listing
July 2022

Impact of Obesity on Microvascular Obstruction and Area at Risk in Patients After ST-Segment-Elevation Myocardial Infarction: A Magnetic Resonance Imaging Study.

Diabetes Metab Syndr Obes 2022 28;15:2207-2216. Epub 2022 Jul 28.

Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: Better survival for overweight and obese patients after ST-segment elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), microvascular obstruction (MVO), and area at risk (AAR) after STEMI was evaluated.

Methods: A prospective observational study was performed to enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for STEMI and cardiac magnetic resonance was performed within 5-7 days. Patients were classified as normal weight (18.5 ≤BMI <24.0 kg/m), overweight (24.0 ≤BMI <28.0 kg/m), or obese (BMI ≥28 kg/m).

Results: Among 225 patients undergoing pPCI, 67 (30.00%) were normal weight, 113 (50.22%) were overweight, and 45 (20.00%) were obese. BMI ≥28 kg/m was significantly associated with less risk of MVO when compared with a normal BMI after multivariable adjustment (overweight: HR 0.29, 95% CI 0.13-0.68, p = 0.004). Compared with normal weight patients, obese and overweight patients tend to have larger hearts (greater left ventricular end-diastolic volume [LVEDV] and left ventricular [LV] mass). In adjusted analysis, increased BMI was significantly associated with a smaller AAR. In addition, obese patients had a smaller AAR (β = -0.252, 95% CI -20.298- -3.244, p = 0.007) and AAR, % LV mass (β = -0.331, 95% CI -0.211- -0.062, p < 0.001) than normal weight patients.

Conclusion: Obesity (BMI ≥28 kg/m) is independently associated with lower risks of MVO and a smaller AAR, % LV mass than normal weight patients among subjects undergoing pPCI for STEMI.
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http://dx.doi.org/10.2147/DMSO.S369222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342698PMC
July 2022

The fault detection of transmitting current encoded by m-sequence using triple-correlation function in helicopter-borne electromagnetic method.

Rev Sci Instrum 2022 Jul;93(7):074501

Key Laboratory of Geo-exploration Instruments, Ministry of Education of China, Changchun 130061, China.

An m-sequence is applied to the helicopter-borne electromagnetic method system for the first time, and there are many problems to be solved, one of which is the detection of the quality of the transmitting current waveform, which directly affects the resource survey results. In this research, we found that the triple-correlation function (TCF) can reveal the bit integrity characteristics of the m-sequence encoded transmitting current. On this basis, this paper proposes to extract the three-dimensional information of the normalized TCF plot by using a peak detection method and, then, proposes to use a dual-threshold method to clarify the detection results. The whole process realizes the fault detection of the transmitting current waveform. We propose a reasonable transmitting current modeling method and conduct 1200 random experiments in 12 groups. The statistics of the experimental results show that when the number of missing bits is 1, 2, 4, and 8, the fault detection accuracy can reach more than 83%. A comparative experiment using the Field Programmable Gate Array. in the laboratory validates the feasibility of the fault detection method. This method is beneficial to improve the quality of detection data and avoid economic losses caused by invalid detection flights.
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http://dx.doi.org/10.1063/5.0090992DOI Listing
July 2022

IPO7 promotes odontoblastic differentiation and inhibits osteoblastic differentiation through regulation of RUNX2 expression and translocation.

Stem Cells 2022 Aug 3. Epub 2022 Aug 3.

The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

RUNX2, an important transcriptional factor for both odontoblastic and osteoblastic differentiation, is upregulated during osteoblastic differentiation, but downregulated during late odontoblastic differentiation. However, the specific mechanism of the different RUNX2 expression in bone and dentin remains largely unknown. Importin 7 (IPO7), a member of the Karyopherin β-superfamily, mediates nucleocytoplasmic transport of proteins. In this study, we found that IPO7 was increasingly expressed from pre-odontoblasts to mature odontoblasts. IPO7 expression was increased with odontoblastic differentiation of mouse dental papilla cells (mDPCs) and knock-down of IPO7 inhibited cell differentiation. While in MC3T3-E1 cells, IPO7 was decreased during osteoblastic differentiation and knock-down of IPO7 promoted cell differentiation. In mPDCs, IPO7 was able to bind with some odontoblastic transcription factors, and imported them into nucleus, but not with RUNX2. Furthermore, IPO7 inhibited the total RUNX2 expression by promoting HDAC6 nuclear localization during odontoblastic differentiation. However, in MC3T3-E1 cells, IPO7 inhibited the nuclear distribution of RUNX2, but did not affect the total protein level of RUNX2. In conclusion, we found that IPO7 promotes odontoblastic differentiation and inhibits osteoblastic differentiation through regulating RUNX2 expression and translocation differently.
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http://dx.doi.org/10.1093/stmcls/sxac055DOI Listing
August 2022

Design of a genetically encoded biosensor to establish a high-throughput screening platform for L-cysteine overproduction.

Metab Eng 2022 Jul 31;73:144-157. Epub 2022 Jul 31.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China; Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. Electronic address:

Metabolic engineering seeks to rewire the metabolic network of cells for the efficient production of value-added compounds from renewable substrates. However, it remains challenging to evaluate and identify strains with the desired phenotype from the vast rational or random mutagenesis library. One effective approach to resolve this bottleneck is to design an efficient high-throughput screening (HTS) method to rapidly detect and analyze target candidates. L-cysteine is an important sulfur-containing amino acid and has been widely used in agriculture, pharmaceuticals, cosmetics, and food additive industries. However, HTS methods that enable monitoring of L-cysteine levels and screening of the enzyme variants and strains to confer superior L-cysteine biosynthesis remain unavailable, greatly limiting the development of efficient microbial cell factories for L-cysteine production at the industrial scale. Here, we took advantage of the L-cysteine-responsive transcriptional regulator CcdR to develop a genetically encoded biosensor for engineering and screening the L-cysteine overproducer. The in vivo L-cysteine-responsive assays and in vitro electrophoretic mobility shift assay (EMSA) and DNase I footprint analysis indicated that CcdR is a transcriptional activator that specifically interacts with L-cysteine and binds to its regulatory region to induce the expression of target genes. To improve the response performance of the L-cysteine biosensor, multilevel optimization strategies were performed, including regulator engineering by semi-rational design and systematic optimization of the genetic elements by modulating the promoter and RBS combination. As a result, the dynamic range and sensitivity of the biosensor were significantly improved. Using this the excellent L-cysteine biosensor, a HTS platform was established by coupling with fluorescence-activated cell sorting (FACS) and was successfully applied to achieve direct evolution of the key enzyme in the L-cysteine biosynthetic pathway to increase its catalytic performance and to screen the high L-cysteine-producing strains from the random mutagenesis library. These results presented a paradigm of design and optimization of biosensors to dynamically detect metabolite concentrations and provided a promising tool enabling HTS and metabolic regulation to construct L-cysteine hyperproducing strains to satisfy industrial demand.
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http://dx.doi.org/10.1016/j.ymben.2022.07.007DOI Listing
July 2022

A ratiometric fluorescent probe based on two-isophorone fluorophore for detecting cysteine.

J Mater Chem B 2022 Aug 3. Epub 2022 Aug 3.

College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China.

The key biological thiol, cysteine (Cys), which can participate in many physiological and pathological processes in the human body, has also been proved to have considerable effects on redox homeostasis and the regulation of cell activity . A large number of studies have shown that abnormal Cys concentration is inseparable from the occurrence of many diseases. Therefore, it is of considerable research value to develop a method to specifically detect Cys. In this study, a new ratiometric fluorescent probe of two-isophorone fluorophore, TIFC, was proposed to successfully detect intracellular Cys by ratiometric fluorescence signals and the results showed that TIFC has good selectivity and sensitivity. The results of biological imaging experiments also demonstrated that probe TIFC can exhibit a rapid ratiometric response to Cys and has low cytotoxicity, enabling high biocompatible fluorescence imaging in osteoblasts. Therefore, TIFC has the potential of rapid ratio-response to Cys for the preliminary diagnosis of related diseases.
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http://dx.doi.org/10.1039/d2tb00882cDOI Listing
August 2022

Preparation of reductive polypeptides from fresh placentas of dairy cows.

Vet Res Forum 2022 Jun 15;13(2):163-168. Epub 2022 Jun 15.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

In order to prepare reductive polypeptides from the placenta of dairy cows' fresh placentas from healthy Chinese Holstein cows were obtained and homogenized. Response surface model was established to optimize the hydrolysis condition for the extraction of the placental polypeptides. Specifically, the placental tissue homogenate was treated with both trypsin and pepsin for 348 min and 329 min; at 35.00% and 35.75% of substrate concentration; with an enzyme-substrate ratio of 3.33% and 3.92%, respectively, based on the models. The treated samples were then demineralized and freeze-dried to obtain the hydrolyzed polypeptides. In order to identify the molecular mass distribution and reducibility of polypeptides, matrix-assisted laser desorption ionization (MALDI) and Prussian blue methods were used. The concentrations of placental polypeptides after hydrolysis by trypsin or pepsin were 5.52% and 5.97%, respectively; the vitamin C (Vit C) equivalents were 36.26 μg mg or 61.15 μg mg, respectively. Both groups showed intensity peaks of MALDI patterns in the range of 300 - 400 Da, and polypeptides hydrolyzed by pepsin had higher Vit C equivalent anti-oxidant activity than trypsin hydrolyzed polypeptide, suggesting that the proteins in the placental tissues were hydrolyzed to di-peptides and tri-peptides completely. In conclusion, both trypsin and pepsin hydrolysis performed well in preparation of reductive polypeptides from the fresh placentas of dairy cows; while, pepsin is more effective than trypsin. The primary reductive ingredients may be the oligopeptides with molecular mass less than 1000 Da.
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http://dx.doi.org/10.30466/vrf.2020.124164.2912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340283PMC
June 2022

Boron Carbon Nitride Nanosheets-Ru Nanocomposite Self-Enhancement Electrochemiluminescence Emitter with a Three-Dimensional DNA Network Structure as a Signal Amplifier for Ultrasensitive Detection of TK1 mRNA.

Anal Chem 2022 Aug 2. Epub 2022 Aug 2.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.

In this study, a neoteric self-enhanced nanocomposite boron carbon nitride nanosheets (BCN NSs)-Ru obtained by chemical crosslinking between boron carbon nitride nanosheets (BCN NSs) and tris (4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)Cl) was used as an emitter to build an electrochemiluminescence (ECL) biosensor for ultrasensitive detection of the cancer marker human thymidine kinase 1 (TK1) mRNA. Importantly, the self-enhanced BCN NSs-Ru could exhibit strong ECL emission because boron radicals and amine groups derived from BCN NSs could significantly enhance the ECL response of Ru(dcbpy)Cl, which avoided the defects of the long electron transfer path and large energy loss between the emitter and coreactant in the traditional coreaction ECL system. Impressively, in the presence of target TK1 mRNA, three-dimensional DNA network structure-labeled numerous ferrocene probes could be assembled to quickly quench the ECL signal of BCN NSs-Ru, resulting in improved biosensor sensitivity. The obtained "on-off" biosensor showed excellent stability and high sensitivity with a detection limit of 32.3 aM. In general, the developed strategy provided a new biosensing way for ultrasensitive detection of biomolecules in early disease diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.2c02110DOI Listing
August 2022

Understanding the factors affecting the surface chemical composition of dairy powders: a systematic review.

Crit Rev Food Sci Nutr 2022 Aug 2:1-15. Epub 2022 Aug 2.

College of Engineering, China Agricultural University, Beijing, China.

Dairy powder, with abundant chemical components such as protein, fat, and lactose possessing diverse physical and chemical structures, can exhibit a surface composition distinct from its bulk content during the conversion of liquid milk into dry powder. Surface chemical composition is a significant parameter in the dairy industry, as it is directly associated with the techno-functional properties of dairy powder products. The current work provides an overview of the factors influencing the surface composition of dairy powders such as the bulk composition of raw milk (animal source and formulation), liquid dairy processing (homogenization, thermal treatment, and evaporation), the drying process (drying methods as well as operating conditions during the most commonly used spray drying), and storage conditions (temperature, relative humidity, and duration). The underlying mechanisms involved in the variations of particle surface composition include the mechanical properties of emulsion, milk fat globules redistribution caused by mechanical forces, adsorption competition and interactions of ingredients at the water/air interface, dehydration-induced alterations in particle structure, corresponding solid/solutes segregation differentiation during spray drying, and lactose crystallization-induced increase in surface fat during storage. Additionally, future research is suggested to explore the effects of emerging processing technologies on the surface composition modification of dairy powders.
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http://dx.doi.org/10.1080/10408398.2022.2105803DOI Listing
August 2022
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