Publications by authors named "Peng Xu"

1,754 Publications

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Roles of lncRNA MAGI2-AS3 in human cancers.

Biomed Pharmacother 2021 Jun 11;141:111812. Epub 2021 Jun 11.

Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Shaanxi 710054, China. Electronic address:

Long noncoding RNAs (lncRNAs) are noncoding RNAs more than 200 nucleotides in length. A growing number of reports indicate that lncRNAs play a key role in multiple cancers by serving as oncogenes or tumor suppressor genes. MAGI2 antisense RNA 3 (MAGI2-AS3) is ubiquitously expressed in human cancers, and the level of MAGI2-AS3 expression is associated with the progression and prognosis of cancers. Moreover, dysregulation of MAGI2-AS3 has been found to regulate cancer cell proliferation, cell death, invasion and metastasis and treatment resistance by serving as a competing endogenous RNA (ceRNA), epigenomic regulator, and transcriptional regulator. Moreover, increasing evidence shows that MAGI2-AS3 may be a potential biomarker for cancer prognosis and a potential target for cancer therapy. In this review, we summarize current research on the functions, mechanisms and clinical significance of the lncRNA MAGI2-AS3 in cancer development.
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http://dx.doi.org/10.1016/j.biopha.2021.111812DOI Listing
June 2021

Lentinan as a natural stabilizer with bioactivities for preparation of drug-drug nanosuspensions.

Int J Biol Macromol 2021 Jun 10;184:101-108. Epub 2021 Jun 10.

School of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address:

Lentinan is a natural β-glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug-drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib-lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib-lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug-drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.056DOI Listing
June 2021

Delayed elimination communication on the prevalence of children's bladder and bowel dysfunction.

Sci Rep 2021 Jun 11;11(1):12366. Epub 2021 Jun 11.

Pediatric Urodynamic Center and Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

To determine the prevalence of bladder and bowel dysfunction (BBD) and its relationship with delayed elimination communication (EC) in children. A cross-sectional study was carried out in kindergartens and primary schools in mainland China. A total of 10,166 children ranging from 4 to 10 years old were included. A total of 10,166 valid questionnaires were collected, and 409 children were diagnosed with BBD. The overall prevalence was 4.02% (409/10,166) and decreased with age, from 6.19% at age 4 to 1.96% at age 10. With the prolonged use of disposable diapers (DDs), the commencement of usage of EC in a child was significantly put off or delayed by parents, and the prevalence of BBD amongst these children increased (P < 0.001). The prevalence of BBD among children who stopped using DDs within the first 12 months and after more than 24 months was 2.79% and 4.38% respectively. Additionally, the prevalence among children who started EC within 12 months after birth and those who never engaged in EC was 1.36% and 15.71% respectively. Early introduction of EC and weaning of DD usage has a positive correlation with lower prevalence of BBD in children in China.
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http://dx.doi.org/10.1038/s41598-021-91704-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196082PMC
June 2021

The Hypertension Related Gene G-Protein Coupled Receptor Kinase 4 Contributes to Breast Cancer Proliferation.

Breast Cancer (Auckl) 2021 20;15:11782234211015753. Epub 2021 May 20.

Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA.

Purpose: Clinical studies have shown that breast cancer risk is increased in hypertensive women. The underlying molecular mechanism remains undetermined. The current study tests our hypothesis that G protein coupled receptor kinase 4 (GRK4) is a molecule that links hypertension and breast cancer. GRK4 plays an important role in regulation of renal sodium excretion. Sustained activation of GRK4 as in the circumstances of single nucleotide polymorphism (SNPs) causes hypertension. Expression of GRK4 in the kidney is regulated by cMyc, an oncogene that is amplified in breast cancer.

Methods: Western analysis was used to evaluate GRK4 protein expression in seven breast cancer cell lines. gene single nucleotide polymorphism in breast cancer cell lines and in breast cancer cDNA arrays were determined using TaqMan Genotyping qPRC. The function of GRK4 was evaluated in MCF-7 cells with cMyc knock-down and GRK4 re-expression and in MDA-MB-468 cells expressing inducible GRK4 shRNA lentivirus constructs. Nuclei counting and 5-Bromo-2'-deoxy-uridine (BrdU) labeling were used to evaluate cell growth and proliferation.

Results: Genotyping of SNPs in breast cancer cDNA arrays (n = 94) revealed that the frequency of carrying two hypertension related SNPs A142 V or R65 L is threefold higher in breast cancer patients than in healthy people ( = 7.53E-11). GRK4 protein is expressed in seven breast cancer cell lines but not the benign mammary epithelial cell line, MCF-10A. Three hypertension related SNPs in the gene were identified in the breast cancer cell lines. Except for BT20, all other breast cancer lines have 1-3 SNPs of which A142 V occurs in all 6 lines. MDA-MB-468 cells contain homozygous A142 V and R65 L SNPs. Knocking down cMyc in MCF-7 cells significantly reduced the growth rate, which was rescued by re-expression of GRK4. We then generated three stable GRK4 knock-down MDA-MB-468 lines using inducible lentiviral shRNA vectors. Doxycycline (Dox) induced GRK4 silencing significantly reduced GRK4 mRNA and protein levels, growth rates, and proliferation. As a marker of cell proliferation, the percentage of BrdU-labeled cells decreased from 45 ± 3% in the cells without Dox to 32 ± 5% in the cells treated with 0.1 µg/mL Dox.

Conclusions: GRK4 acts as an independent proliferation promotor in breast cancer. Our results suggest that targeted inhibition of GRK4 could be a new therapy for both hypertension and breast cancer.
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http://dx.doi.org/10.1177/11782234211015753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145586PMC
May 2021

Ubiquitin-related molecular classification and risk stratification of hepatocellular carcinoma.

Mol Ther Oncolytics 2021 Jun 17;21:207-219. Epub 2021 Apr 17.

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

The roles of ubiquitin-related genes in hepatocellular carcinoma (HCC) have not been thoroughly investigated. This study aimed to systematically examine ubiquitin-related genes and identify subtypes and stratify prognosis of HCC by using ubiquitin-related signatures. Survival, biological processes, tumor microenvironment (TME), and genomic alterations of the HCC subtypes were investigated. Patients with HCC were classified into two subtypes (clusters 1 and 2) with distinct survival outcomes, pathways, and genomic alterations. Cluster 2 had better prognosis than did cluster 1. Hepatitis B, hepatitis C, Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, and natural killer cell-mediated cytotoxicity were enriched in cluster 1. Moreover, cluster 2 had a higher immune score and immune cell infiltrations, whereas cluster 1 had a lower immune score and immune infiltrations. Additionally, mutations, amplifications, and deletions among the phosphatidylinositol 3-kinase (PI3K)-AKT, p53, and receptor tyrosine kinase (RTK)-RAS pathways more frequently occurred in cluster 1, while those among the Hippo, MYC, and Notch signaling pathways were found in cluster 2. Finally, a prognostic signature, consisting of eight ubiquitin-related genes, was established and validated. In brief, our study established a new classification and developed a prognostic signature for HCC.
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http://dx.doi.org/10.1016/j.omto.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138213PMC
June 2021

Interphase epichromatin: last refuge for the 30-nm chromatin fiber?

Chromosoma 2021 Jun 5. Epub 2021 Jun 5.

Department of Pharmaceutical Sciences and Administration, School of Pharmacy, University of New England, 716 Stevens Avenue, Portland, ME, 04103, USA.

"Interphase epichromatin" describes the surface of chromatin located adjacent to the interphase nuclear envelope. It was discovered in 2011 using a bivalent anti-nucleosome antibody (mAb PL2-6), now known to be directed against the nucleosome acidic patch. The molecular structure of interphase epichromatin is unknown, but is thought to be heterochromatic with a high density of "exposed" acidic patches. In the 1960s, transmission electron microscopy of fixed, dehydrated, sectioned, and stained inactive chromatin revealed "unit threads," frequently organized into parallel arrays at the nuclear envelope, which were interpreted as regular helices with ~ 30-nm center-to-center distance. Also observed in certain cell types, the nuclear envelope forms a "sandwich" around a layer of closely packed unit threads (ELCS, envelope-limited chromatin sheets). Discovery of the nucleosome in 1974 led to revised helical models of chromatin. But these models became very controversial and the existence of in situ 30-nm chromatin fibers has been challenged. Development of cryo-electron microscopy (Cryo-EM) gave hope that in situ chromatin fibers, devoid of artifacts, could be structurally defined. Combining a contrast-enhancing phase plate and cryo-electron tomography (Cryo-ET), it is now possible to visualize chromatin in a "close-to-native" situation. ELCS are particularly interesting to study by Cryo-ET. The chromatin sheet appears to have two layers of ~ 30-nm chromatin fibers arranged in a criss-crossed pattern. The chromatin in ELCS is continuous with adjacent interphase epichromatin. It appears that hydrated ~ 30-nm chromatin fibers are quite rare in most cells, possibly confined to interphase epichromatin at the nuclear envelope.
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http://dx.doi.org/10.1007/s00412-021-00759-8DOI Listing
June 2021

Balanced Distribution Adaptation for Metal Oxide Semiconductor Gas Sensor Array Drift Compensation.

Sensors (Basel) 2021 May 13;21(10). Epub 2021 May 13.

School of Electrical Engineering and Automation, Harbin Institute of Technology, Harbin 150001, China.

Drift compensation is an important issue for metal oxide semiconductor (MOS) gas sensor arrays. General machine learning methods require constant calibration and a large amount of label gas data. At the same time, recalibration will cause a lot of costs, and label gas is difficult to obtain in practice. In this paper, a novel drift compensation method based on balanced distribution adaptation (BDA) is proposed. First, the BDA drift compensation method can adjust the conditional distribution and marginal distribution between the two domains through the weight balance factor, thereby more effectively reducing the mismatch between the two domains. When the BDA method performs classification tasks through machine learning, no labeled data is required in the target domain. Then, the particle swarm optimization algorithm is used to improve the accuracy of drift compensation. Individuals in the population are initialized randomly, and their fitness values are calculated. Iterative optimization of the population individuals is conducted until the optimal weight balance factor parameters are calculated. Finally, the BDA method is experimentally verified on the public gas sensor drift data set. Experimental results showed that the BDA method was significantly better than the existing joint distribution adaptation (JDA) method and other standard drift compensation methods such as K-Nearest Neighbor (KNN). In the two setting groups, the recognition accuracy was 4.54% and 1.62% ahead of the JDA method, and 12.23% and 15.83% ahead of the KNN method.
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http://dx.doi.org/10.3390/s21103403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153337PMC
May 2021

Altered Functional Connectivity in Children with ADHD Revealed by Scalp EEG: An ERP Study.

Neural Plast 2021 11;2021:6615384. Epub 2021 May 11.

School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental brain disorders in childhood. Despite extensive researches, the neurobiological mechanism underlying ADHD is still left unveiled. Since the deficit functions, such as attention, have been demonstrated in ADHD, in our present study, based on the oddball P3 task, the corresponding electroencephalogram (EEG) of both healthy controls (HCs) and ADHD children was first collected. And we then not only focused on the event-related potential (ERP) evoked during tasks but also investigated related brain networks. Although an insignificant difference in behavior was found between the HCs and ADHD children, significant electrophysiological differences were found in both ERPs and brain networks. In detail, the dysfunctional attention occurred during the early stage of the designed task; as compared to HCs, the reduced P2 and N2 amplitudes in ADHD children were found, and the atypical information interaction might further underpin such a deficit. On the one hand, when investigating the cortical activity, HCs recruited much stronger brain activity mainly in the temporal and frontal regions, compared to ADHD children; on the other hand, the brain network showed atypical enhanced long-range connectivity between the frontal and occipital lobes but attenuated connectivity among frontal, parietal, and temporal lobes in ADHD children. We hope that the findings in this study may be instructive for the understanding of cognitive processing in children with ADHD.
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http://dx.doi.org/10.1155/2021/6615384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133851PMC
May 2021

Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation.

Front Pharmacol 2021 14;12:672054. Epub 2021 May 14.

Department of Joint Surgery, Xi'an Jiaotong University Affiliated HongHui Hospital, Xi'an, China.

Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent hyperplasia of the synovial membrane and progressive erosion of articular cartilage. Disequilibrium between the proliferation and death of RA fibroblast-like synoviocytes (RA-FLSs) is the critical factor in progression of RA. Naringin has been reported to exert anti-inflammatory and antioxidant effect in acute and chronic animal models of RA. However, the therapeutic effect and underlying mechanisms of naringin in human RA-FLS remain unclear. Based on network pharmacology, the corresponding targets of naringin were identified using SwissTargetPrediction database, STITCH database, and Comparative Toxicogenomics Database. Deferentially expressed genes (DEGs) in RA were obtained from the GEO database. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to pathogenesis of RA were integrated manually. Further, studies were carried out based on network pharmacology. 99 target genes were intersected between targets of naringin and DEGs. The PPI network and topological analysis indicated that IL-6, MAPK8, MMP-9, TNF, and MAPK1 shared the highest centrality among all. GO analysis and KEGG analysis indicated that target genes were mostly enriched in (hsa05200) pathways in cancer, (hsa05161) hepatitis B, (hsa04380) osteoclast differentiation, (hsa04151) PI3K-Akt signaling pathway, and (hsa05142) Chagas disease (American trypanosomiasis). studies revealed that naringin exposure was found to promote apoptosis of RA-FLS, increased the activation of caspase-3, and increased the ratio of Bax/Bcl-2 in a dose-dependent manner. Furthermore, treatment of naringin attenuated the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in TNF-ɑ-induced RA-FLS. Moreover, treatment of naringin inhibited the phosphorylation of Akt and ERK in RA-FLS. Network pharmacology provides a predicative strategy to investigate the therapeutic effects and mechanisms of herbs and compounds. Naringin inhibits inflammation and MMPs production and promotes apoptosis in RA-FLS PI3K/Akt and MAPK/ERK signaling pathways.
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http://dx.doi.org/10.3389/fphar.2021.672054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160516PMC
May 2021

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis.

Front Pharmacol 2021 13;12:609901. Epub 2021 May 13.

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

The prevalence rate of hypertension and breast cancer increases with advancing age. Renin-angiotensin system inhibitors (RASIs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics are widely used to treat patients with hypertension. Although, the association between the use of antihypertensive medication and breast cancer has been highly debated, recent evidence supporting this association remains controversial. To evaluate the association between the use of antihypertensive medication and the risk of breast cancer and its prognosis. This study was conducted using data from the PubMed, Embase, and Cochrane Library databases retrieved for the period from January 2000 to April 2021. Articles and their references were checked and summary effects were calculated using random- and fixed-effects models. Heterogeneity test and sensitivity analysis were also performed. This meta-analysis included 57 articles, which were all related to breast cancer risk or prognosis. Assessment of breast cancer risk using the pooled data showed that the use of BBs or CCBs or diuretics was associated with increased cancer risk [BB: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.09-1.32; CCBs: RR = 1.06, 95% CI 1.03-1.08; diuretics: RR = 1.06, 95% CI 1.01-1.11]. Long-term use of diuretic increased the risk of breast cancer (RR = 1.10, 95% CI 1.01-1.20), whereas long-term RASIs treatment reduced the risk (RR = 0.78, 95% CI 0.68-0.91). In addition, we found that diuretic users may be related to elevated breast cancer-specific mortality [hazard ratio (HR) = 1.18, 95% CI 1.04-1.33], whereas using other antihypertensive medications was not associated with this prognosis in patients with breast cancer. Using CCBs, BBs, and diuretics increased the risk of breast cancer. In addition, diuretics may elevate the risk of breast cancer-specific mortality. The long-term use of RASIs was associated with a significantly lower breast cancer risk, compared with non-users. Thus, this analysis provides evidence to support the benefits of the routine use of RASIs in patients with hypertension, which has important public health implications.
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http://dx.doi.org/10.3389/fphar.2021.609901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155668PMC
May 2021

Blue light-dependent interactions of CRY1 with GID1 and DELLA proteins regulate gibberellin signaling and photomorphogenesis in Arabidopsis.

Plant Cell 2021 May 6. Epub 2021 May 6.

Shanghai Key Laboratory of Plant Molecular Sciences, College of Life Sciences, Shanghai Normal University, Shanghai 200234, China.

Cryptochromes are blue light photoreceptors that mediate various light responses in plants and mammals. In Arabidopsis (Arabidopsis thaliana), cryptochrome 1 (CRY1) mediates blue light-induced photomorphogenesis, which is characterized by reduced hypocotyl elongation and enhanced anthocyanin production, whereas gibberellin (GA) signaling mediated by the GA receptor GA-INSENSITIVE DWARF1 (GID1) and DELLA proteins promotes hypocotyl elongation and inhibits anthocyanin accumulation. Whether CRY1 control of photomorphogenesis involves regulation of GA signaling is largely unknown. Here, we show that CRY1 signaling involves the inhibition of GA signaling through repression of GA-induced degradation of DELLA proteins. CRY1 physically interacts with DELLA proteins in a blue light-dependent manner, leading to their dissociation from SLEEPY1 (SLY1) and the inhibition of their ubiquitination. Moreover, CRY1 interacts directly with GID1 in a blue light-dependent but GA-independent manner, leading to the inhibition of the interaction between GID1 with DELLA proteins. These findings suggest that CRY1 controls photomorphogenesis through inhibition of GA-induced degradation of DELLA proteins and GA signaling, which is mediated by CRY1 inhibition of the interactions of DELLA proteins with GID1 and SCFSLY1, respectively.
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http://dx.doi.org/10.1093/plcell/koab124DOI Listing
May 2021

[Reliability of tibial anterior crest as the anatomical reference of rotating alignment for tibial component in total knee arthroplasty].

Zhongguo Gu Shang 2021 May;34(5):417-24

Osteonecrosis and Joint Reconstruction Ward, Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi, China.

Objective: This study aimed to research whether anterior tibial crest is a reliable anatomical reference for rotational alignment of tibial component in TKA.

Methods: The study included 122 patients who underwent computed tomography angiography (CTA) examination for unilateral lower extremity trauma with normal contralateral lower extremities, including 89 males and 33 females, with an average age of(51.4±16.4) years old(ranged 18 to 81 years old). Picture archiving and communication system (PACS) was used to mark 11 lines including the surgical epicondylar axis (SEA) connecting the most prominent points of the lateral epicondyle and the deepest point of the sulcus on the medial epicondyle of the femur, axis of medial border of patellar tendon (MEPT)connecting the middle of the posterior cruciate ligament (PCL) and medial border of the patellar tendon at the level of a standard tibial cut from 8 mm distal of the lateral tibial joint surface, transverse axis of tibia (TAT) at the level of a standard tibial cut from 8 mm distal of the lateral tibial joint surface, Akagi line connecting the projected middle of the PCL and medial border of the patellar tendon at the tibial attachment, the axis of the medial 1/3 of patellar tendon(M1/3) connecting the projected middle of PCL and the medial 1/3 of the patellar tendon at the patellar tendon attachment level, Insall line connecting the projected middle of the PCL and the medial 1/3 of tibial tubercle, the axis of medial border of tibial tubercle (MBTT) connecting the projected middle of the PCL and medial border of tibial tubercle, as well as the axis of the proximal anterior tibial crest (PATC), axis 1 of the middle anterior tibial crest (MATC1), axis 2 of the middle anterior tibial crest (MATC2) and the axis of the distal anterior tibial crest (DATC) which were marked by connecting the 4 equidistant points on the sharp anterior tibial crest and the projected middle of the PCL. The angles between TAT and SEA as well as the angles between other axes and the perpendicular to SEA were measured. Pairwise differences among the 10 tibial axes were examined using One-Way ANOVA and paired -test.

Results: The angles between the axes of MEPT, Akagi line, M1/3, Insall line, MBTT, PATC, MATC1, MATC2, DATC and the perpendicular to SEA were (-1.6 ±4.5)° , (1.4 ±5.0)° , (10.2±5.1)°, (11.9±5.4)°, (3.6±4.8)°, (12.0±6.9)°, (7.2±8.6)°, (7.1±10.4)°, (6.6±13.5)°, respectively. The angle between TAT and SEA was (4.1±5.3)°. MEPT was external rotation compared to SEA. M1/3, Insall line and PATC were significantly greater than Akagi line, MBTT, TAT (<0.001). MATC1, MATC2 and DATC were also significantly greater than Akagi line, MBTT axis and TAT (<0.001). However, MATC1, MATC2 and DATC were also significantly less than M1/3 axis, Insall line and PATC(<0.01). There were no significant statistical differences between MATC1, MATC2 and DATC(>0.05).

Conclusion: The middle tibial anterior crest can be used as a reference for rotational alignment of tibial component in TKA, and its reliability is better than Insall line, but worse than Akagi line, TAT and MBTT.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.05.005DOI Listing
May 2021

Enhanced 4-FP removal with MnFeO catalysts under dielectric barrier discharge plasma: Economical synthesis, catalytic performance and degradation mechanism.

J Hazard Mater 2021 07 6;414:125602. Epub 2021 Mar 6.

College of Resource and Environment, Qingdao Engineering Research Center for Rural Environment, Qingdao Agricultural University, Qingdao 266109, PR China. Electronic address:

The dielectric barrier discharge plasma (DBDP) process has received extensive attention for the removal of organic contaminants from water. A novel microwave-assisted hydrothermal method was used to easily and rapidly synthesize MnFeO catalysts. Based on the DBDP process, MnFeO can enhance 4-fluorophenol (4-FP) abatement from 44.15% to 58.78% through the catalysis within 18 min. Then, the adjunction of O generated by discharge can further boost 4-FP degradation to 94.94%. After the whole optimization process is complete, the associated pseudo-first-order reaction kinetic constant and energy efficiency were enhanced from 0.0327 to 0.1536 min and 2067.13 mg kW h to 4444.75 mg kW h, respectively. With the help of the condition, blank and radical capture experiments, the catalytic performance caused by MnFeO and O was attributed to the joint action of Fenton-like reactions, photocatalysis (ultraviolet, UV), photoassisted Fenton reactions and O catalysis. The overall downward trend of the possible intermediate toxicities indicated that the DBDP/MnFeO/O process can effectively remove and mineralize 4-FP without the generation of more toxic intermediates. In addition, during the 5 cycles, MnFeO can maintain excellent recovery, efficiency and durability. In summary, the coupling of discharge plasma and MnFeO sheds new light on catalysis for wastewater treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125602DOI Listing
July 2021

Cellular and Molecular Processes in Pulmonary Hypertension.

Adv Exp Med Biol 2021 ;1304:21-38

Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA.

Pulmonary hypertension (PH) is a progressive lung disease characterized by persistent pulmonary vasoconstriction. Another well-recognized characteristic of PH is the muscularization of peripheral pulmonary arteries. This pulmonary vasoremodeling manifests in medial hypertrophy/hyperplasia of smooth muscle cells (SMCs) with possible neointimal formation. The underlying molecular processes for these two major vascular responses remain not fully understood. On the other hand, a series of very recent studies have shown that the increased reactive oxygen species (ROS) seems to be an important player in mediating pulmonary vasoconstriction and vasoremodeling, thereby leading to PH. Mitochondria are a primary site for ROS production in pulmonary artery (PA) SMCs, which subsequently activate NADPH oxidase to induce further ROS generation, i.e., ROS-induced ROS generation. ROS control the activity of multiple ion channels to induce intracellular Ca release and extracellular Ca influx (ROS-induced Ca release and influx) to cause PH. ROS and Ca signaling may synergistically trigger an inflammatory cascade to implicate in PH. Accordingly, this paper explores the important roles of ROS, Ca, and inflammatory signaling in the development of PH, including their reciprocal interactions, key molecules, and possible therapeutic targets.
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http://dx.doi.org/10.1007/978-3-030-68748-9_2DOI Listing
May 2021

Tracheal, bronchus, and lung cancer burden and related risk factors in the United States and China.

Am J Transl Res 2021 15;13(4):1928-1951. Epub 2021 Apr 15.

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China.

Tracheal, bronchus, and lung (TBL) cancer is the most common malignant tumor worldwide. This study aims to grasp the characteristics of the TBL cancer burden in China and the United States (USA). Data included incidence, deaths, and disability-adjusted life years (DALYs) as well as their age-standardized rates (ASRs) among different gender, age and risk factors. Joinpoint Regression Model and Age-period-cohort (APC) analysis were used to evaluate the variation tendency and effect of the risk factors. China and USA bore almost half of the TBL cancer burden, especially for males. ASRs of TBL cancer increased in China, but decreased in USA. In China, three factors related to TBL cancer deaths and DALYs related were tobacco, air pollution, and diet low in fruits; in USA, these are tobacco, occupational carcinogens, and high fasting plasma glucose. The younger the population, the less impact of birth cohort on morbidity and mortality. According to APC analysis, age effect played a key role in morbidity and mortality of TBL cancer, and the risk increased with age. Period effect kept increasing over time, while cohort effect decreased with the time of birth. Tobacco was always the top risk factor of death and DALYs in both countries. The policy should be tilted towards air pollution and a diet low in fruits in China, as well as occupational carcinogens and high fasting plasma glucose in USA. Healthcare reform in both countries should focus on planning how its health system could effectively prevent and manage TBL cancer at low cost.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129289PMC
April 2021

Conferring thermotolerant phenotype to wild-type Yarrowia lipolytica improves cell growth and erythritol production.

Biotechnol Bioeng 2021 May 19. Epub 2021 May 19.

School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.

In microbial engineering, heat stress is an important environmental factor modulating cell growth, metabolic flux distribution and the synthesis of target products. Yarrowia lipolytica, as a GARS (generally recognized as safe) nonconventional yeast, has been widely used in the food industry, especially as the host of erythritol production. Biomanufacturing economics is limited by the high operational cost of cooling energy in large-scale fermentation. It is of great significance to select thermotolerant Y. lipolytica to reduce the cooling cost and elucidate the heat-resistant mechanism at molecular level. For this purpose, we performed adaptive evolution and obtained a thermotolerant strain named Y. lipolytica BBE-18. Transcriptome analysis allows us to identify four genes in thiamine metabolism pathway that are responsible for the complicated thermotolerant phenotype. The heat-resistant phenotype was validated with the model strain Y. lipolytica Po1f by overexpression of single and combined genes. Then, conferring the thermotolerant phenotype to the wild-type Y. lipolytica BBE-17 enable the strain to produce three-times more erythritol of the control strain with 3°C higher than optimal cultivation temperature. To our knowledge, this is the first report on engineering heat-resistant phenotype to improve the erythritol production in Y. lipolytica. However, due to the increase of culture temperature, a large amount of adenosine triphosphate is consumed to ensure the life activities of Y. lipolytica which limits the potential of cell synthetic products to a certain extent. Even so, this study provides a reference for Y. lipolytica to produce other products under high temperature.
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http://dx.doi.org/10.1002/bit.27835DOI Listing
May 2021

Enhanced antibiotic treatment based on positive urine dipstick infection test before percutaneous nephrolithotomy did not prevent postoperative infection in patients with negative urine culture.

J Endourol 2021 May 18. Epub 2021 May 18.

Minimally Invasive Surgery center, The first affiliated Hospital of Guangzhou medical University, Urology, kangda Road 1#,, Haizhu District, Guangzhou, Guangdong, China, 510230;

Introduction: Urinary tract infection (UTI) should be treated before percutaneous nephrolithotomy (PCNL). However, the most appropriate treatment strategy in patients with negative urine culture but positive urine dipstick infection test (positive urinary leukocyte or nitrite reaction) remains unclear.

Methods: From August 2016 to February 2018, 806 consecutive patients who had undergone the first-stage PCNL with negative urine culture were included. Preoperative urinalysis, antibiotic treatment, intraoperative stone culture, and postoperative systemic inflammatory response syndrome (SIRS) were prospectively recorded. The primary outcome was SIRS. The impact of preoperative antibiotics on preoperative urinary tract infection, stone culture, and postoperative SIRS was studied.

Results: Among the 806 participants, the rate of positive urine dipstick infection test and SIRS were 26.8% and 7.2%, respectively. In univariable analysis, positive urinary nitrite (p<0.001), positive urinary leukocytes (p<0.001), positive urine dipstick infection test (p<0.001), longer duration of pre-PCNL antibiotics (p=0.001), higher level of pre-PCNL antibiotics (p=0.010), infection stones (p=0.001), and positive stone culture (p<0. 001) were risk factors for SIRS. However, multivariable analysis showed that positive stone culture (p=0.004) and prolonged preoperative treatment with antibiotics (p=0.021) were independent risk factors for SIRS. Although preoperative antibiotics reduced the incidence of positive urine leukocyte (p<0.001) or nitrite reactions (p<0.001), prolonged or upgraded preoperative antibiotics did not affect the incidence of positive stone culture. Whether stone culture was positive (p=0.023) or negative (p=0.025), prolonged preoperative treatment with antibiotics was associated with a higher incidence of SIRS.

Conclusions: Enhanced preoperative antibiotic treatment based on positive urine dipstick infection tests was insufficient to reduce the incidence of positive stone culture but increased the risk of SIRS after PCNL in patients with negative urine cultures.
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http://dx.doi.org/10.1089/end.2021.0185DOI Listing
May 2021

Lambda-cyhalothrin and its common metabolite differentially modulate thyroid disruption effects in Chinese lizards (Eremias argus).

Environ Pollut 2021 May 12;287:117322. Epub 2021 May 12.

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing RD 18, Beijing, 100085, China; University of Chinese Academy of Sciences, Yuquan RD 19 a, Beijing, 100049, China. Electronic address:

Although the thyroid effects of pyrethroids on non-target organisms have been well studied, research on the toxic effects of pyrethorid metabolites is still limited. In this study, a type of representative Chinese lizards was used as the model and exposed to environmentally relevant concentrations of lambda-cyhalothrin (LCT) and 3-phenoxybenzoic acid (PBA) through cultivation on 3 and 15 μg/g soil to evaluate and compare their disruption effects on lizard hypothalamus-pituitary-thyroid (HPT) axis. The alterations occurred in lizards were examined through histopathology analyses, hormone level and gene expression measurements, the molecular binding interactions were analyzed in silico as well. The results showed that LCT exposure increased the plasma triiodothyronine (T3), thyroxine (T4) levels and the follicular epithelium heights of thyroid glands, whereas PBA induced no or much less degree of alterations. The ugt and dio2 gene expression in lizard liver was significantly up-regulated by LCT, but PBA caused less or opposite effects. The in silico homology simulation illustrated that LCT binds to TRα in the similar way of T3, while PBA binds to TRβ in the same manner of T3. The results demonstrated that both LCT and its metabolite-PBA could disrupt lizard HPT axis but through distinct mechanisms. The information would facilitate the comprehensive environmental safety assessment of pyrethroids.
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http://dx.doi.org/10.1016/j.envpol.2021.117322DOI Listing
May 2021

SET knockdown attenuated phenotype modulation and calcium channel associated markers of airway smooth muscle cells in asthmatic mice.

Ann Transl Med 2021 Apr;9(8):657

Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, China.

Background: Dysfunctional phenotype modulation and calcium channels in airway smooth muscle cells (ASMCs) are important characteristics of airway remodeling in chronic asthma. However, the mechanisms underlying these pathological processes remain unclear. SET (I2PP2A, inhibitor-2 of protein phosphatase 2A) has many significant functions and is involved in various physiological and pathological processes. This study aimed to determine the function of SET in chronic asthma.

Methods: BALB/c mice were sensitized by ovalbumin injection and repeated inhalation of ovalbumin. The Penh value was measured using the Buxco whole body plethysmography system. A short hairpin RNA of the SET gene was designed and transfected into ASMCs derived from asthmatic mice. Flow cytometry of Annexin-V/propidium iodide staining was used for evaluating cell apoptosis. Western blot was adopted to measure the expression levels of ASMCs phenotype modulation markers and calcium channel-associated proteins.

Results: The results showed that shRNA targeting SET significantly decreased the expression of SET, and enhanced the apoptosis of ASMCs. SET knockdown promoted the expression of contractile phenotype markers such as α-SMA (alpha smooth muscle Actin), SM-MHC (smooth muscle Myosin heavy chain), and calponin, and inhibited the expression of synthetic phenotype markers including vimentin and CD44. The expression of the calcium channel-related proteins STIM1 (Stromal interaction molecule 1) and Orai1 were also inhibited after SET knockdown.

Conclusions: These data demonstrated that SET participated in the development of airway dysfunction in asthma, suggesting that the silencing of SET may be a new therapeutic target for the treatment of asthma patients.
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http://dx.doi.org/10.21037/atm-21-573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106076PMC
April 2021

Discovery and Validation of Circulating EVL mRNA as a Prognostic Biomarker in Pancreatic Cancer.

J Oncol 2021 20;2021:6656337. Epub 2021 Apr 20.

Clinic Medical College, Yangzhou University, Yangzhou 225000, China.

Background: Circulating plasma mRNAs can be analyzed to identify putative cancer biomarkers. This study was conducted in an effort to detect plasma mRNA biomarkers capable of predicting pancreatic cancer (PACA) patient prognosis. . First, prognostic mRNAs that were differentially expressed in PACA in The Cancer Genome Atlas (TCGA) were established, after which microarray expression profiles from PACA patient plasma samples were utilized to specifically identify potential prognostic plasma mRNA biomarkers associated with this cancer type. In total, plasma samples were then collected from 79 PACA patients and 19 healthy controls to confirm differential mRNA expression via qPCR, while Kaplan-Meier analyses were used to examine the link between mRNA expression and patient overall survival.

Results: In total, three prognostic differentially expressed genes were identified in PACA patient plasma samples, including SMAP2, PTPN6, and EVL (Ena/VASP-like). Plasma EVL levels were confirmed via qPCR to be correlated with tumor pathology ( < 0.01), while the overall survival of patients with low plasma EVL levels was poor ( < 0.01). Multivariate Cox regression analyses further confirmed that plasma EVL levels were independent predictors of PACA patient prognosis.

Conclusion: We found that PACA is associated with the downregulation of plasma EVL mRNA levels, indicating that this mRNA may be a viable biomarker associated with patient prognosis.
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http://dx.doi.org/10.1155/2021/6656337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079208PMC
April 2021

Phytochrome B interacts with SWC6 and ARP6 to regulate H2A.Z deposition and photomorphogensis in Arabidopsis.

J Integr Plant Biol 2021 May 13. Epub 2021 May 13.

Shanghai Key Laboratory of Plant Molecular Sciences, College of Life Sciences, Shanghai Normal University, Shanghai, 200234, China.

Light serves as a crucial environmental cue that modulates plant growth and development, which is controlled by multiple photoreceptors including the primary red light photoreceptor, phytochrome B (phyB). The signaling mechanism of phyB involves direct interactions with a group of basic helix-loop-helix (bHLH) transcription factors, PHYTOCHROME-INTERACTING FACTORS (PIFs), and the negative regulators of photomorphogenesis, COP1 and SPAs. H2A.Z is an evolutionarily conserved H2A variant that plays essential roles in transcriptional regulation. The replacement of H2A with H2A.Z is catalyzed by the SWR1 complex. Here, we show that the Pfr form of phyB physically interacts with the SWR1 complex subunits SWC6 and ARP6. phyB and ARP6 co-regulate numerous genes in the same direction, some of which are associated with auxin biosynthesis and response including YUC9, which encodes a rate-limiting enzyme in the tryptophan-dependent auxin biosynthesis pathway. Moreover, phyB and HY5/HYH act to inhibit hypocotyl elongation partially through repression of auxin biosynthesis. Based our findings and previous studies, we propose that phyB promotes H2A.Z deposition at YUC9 to inhibit its expression through direct phyB-SWC6/ARP6 interactions, leading to repression of auxin biosynthesis, and thus inhibition of hypocotyl elongation in red light. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jipb.13111DOI Listing
May 2021

Comparison of bipolar plasmakinetic resection of prostate versus photoselective vaporization of prostate by a three year retrospective observational study.

Sci Rep 2021 May 12;11(1):10142. Epub 2021 May 12.

Department of Urology, The Second Xiangya Hospital of Central South University, Renmin Middle Road 139, Changsha, 410011, China.

Comprehensive evaluation of photoselective vaporization of the prostate (PVP) versus plasmakinetic resection of the prostate (PKRP) in treating benign prostatic hyperplasia (BPH) is inadequate. This single-centre, retrospective observational study was designed to compare their efficacy, complications and sexual function. A total of 215 patients under PVP or PKRP were included in the study, propensity score matching (PSM) was performed to match the baseline characteristics of the two groups, and perioperative and three-year follow-up data were compared between them. Finally, 120 patients (60 for PVP and 60 for PKRP) were matched after PSM. Compared with the PKRP group, the intraoperative haemoglobin loss was lower (9.08 vs 13.75 g/L, P < 0.001) and the duration of catheterization and postoperative hospital stay were shorter (2.97 vs 4.10 day, P < 0.001; 3.95 vs 5.13 day, P < 0.001, respectively), but the operation time was longer (56.72 vs 49, 90 min, P < 0.001) in the PVP group. Urination measurements were improved for both groups after surgery, although no significant differences were found between them during follow-up. Sexual function after surgery was partly increased; however, frequent retrograde and discomfortable ejaculation occurred in both groups. In addition, dysuria incidence and retreatment were higher in the PVP group at 12 months. In conclusion, PVP is safe and effective in relieving BPH-related lower urinary tract symptoms with less perioperative blood loss and earlier recovery without inferior sexual function effects. However, the study is potentially affected by residual unmeasured confounding.
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http://dx.doi.org/10.1038/s41598-021-89623-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115102PMC
May 2021

Mechanisms and detection methods of Mycobacterium tuberculosis rifampicin resistance: The phenomenon of drug resistance is complex.

Tuberculosis (Edinb) 2021 May 8;128:102083. Epub 2021 May 8.

Key Laboratory of Characteristic Infectious Disease & Bio-safety Development of Guizhou Province Education Department, Institute of Life Sciences, Zunyi Medical University, No.6 West Xuefu Road, Xinpu District, Zunyi, Guizhou Province, 563000, China. Electronic address:

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. Rifampin (RIF) is an important first-line anti-TB drug, and rifampin resistance (RIF-R) is a key factor in formulating treatment regimen and evaluating the prognosis of TB. Compared with other drugs resistance, the RIF-R mechanism of Mycobacterium tuberculosis (M. tuberculosis) is one of the clearest, which is mainly caused by RIF resistance-related mutations in the rpoB gene. This provides a convenient condition for developing rapid detection methods, and also an ideal object for studying the general drug resistance mechanisms of M. tuberculosis. This review focuses on the mechanisms that influence the RIF resistance of M. tuberculosis and related detection methods. Besides the mutations in rpoB, M. tuberculosis can decrease the amount of drugs entering the cells, enhance the drugs efflux, and be heterogeneous RIF susceptibility to resist drug pressure. Based on the results of current researches, many genes participate in influencing the susceptibility to RIF, which indicates the phenomenon of M. tuberculosis drug resistance is very complex.
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http://dx.doi.org/10.1016/j.tube.2021.102083DOI Listing
May 2021

POSTN Promotes the Proliferation of Spermatogonial Cells by Activating the Wnt/β-Catenin Signaling Pathway.

Reprod Sci 2021 May 6. Epub 2021 May 6.

Department of Stem Cells and Regenerative Medicine, Shenyang Key Laboratory of Stem Cell and Regenerative Medicine, China Medical University, Shenyang, 110013, Liaoning, China.

The self-renewal of spermatogonial cells (SCs) provides the foundation for life-long spermatogenesis. To date, only a few growth factors have been used for the culture of SCs in vitro, and how to enhance proliferation capacity of SCs in vitro needs further research. This study aimed to explore the effects of periostin (POSTN) on the proliferation of human SCs. GC-1 spg cells were cultured in a medium with POSTN, cell proliferation was evaluated by MTS analysis and EdU assay, and the Wnt/β-catenin signaling pathway was examined. Thereafter, the proliferations of human SC were detected using immunofluorescence and RT-PCR. In this study, we found that CM secreted by human amniotic mesenchymal stem cells (hAMSCs) could enhance the proliferation capacity of mouse GC-1 spg cells. Label-free mass spectrometry and ELISA analysis demonstrated that high level of POSTN was secreted by hAMSCs. MTS and EdU staining showed that POSTN increased GC-1 spg cell proliferation, whereas CM from POSTN-silenced hAMSCs suppressed cell proliferation capacity. Then POSTN was found to activate the Wnt/β-catenin signaling pathway to regulate the proliferation of GC-1 spg cells. XAV-939, a Wnt/β-catenin inhibitor, partially reversed the effects of POSTN on GC-1 spg cell proliferation. We then analyzed human SCs and found that POSTN promoted human SC proliferation in vitro. These findings provide insights regarding the role of POSTN in regulating SC proliferation via the Wnt/β-catenin signaling pathway and suggest that POSTN may serve as a cytokine for male infertility therapy.
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http://dx.doi.org/10.1007/s43032-021-00596-1DOI Listing
May 2021

Single-nucleotide-level mapping of DNA regulatory elements that control fetal hemoglobin expression.

Nat Genet 2021 Jun 6;53(6):869-880. Epub 2021 May 6.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Pinpointing functional noncoding DNA sequences and defining their contributions to health-related traits is a major challenge for modern genetics. We developed a high-throughput framework to map noncoding DNA functions with single-nucleotide resolution in four loci that control erythroid fetal hemoglobin (HbF) expression, a genetically determined trait that modifies sickle cell disease (SCD) phenotypes. Specifically, we used the adenine base editor ABEmax to introduce 10,156 separate A•T to G•C conversions in 307 predicted regulatory elements and quantified the effects on erythroid HbF expression. We identified numerous regulatory elements, defined their epigenomic structures and linked them to low-frequency variants associated with HbF expression in an SCD cohort. Targeting a newly discovered γ-globin gene repressor element in SCD donor CD34 hematopoietic progenitors raised HbF levels in the erythroid progeny, inhibiting hypoxia-induced sickling. Our findings reveal previously unappreciated genetic complexities of HbF regulation and provide potentially therapeutic insights into SCD.
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http://dx.doi.org/10.1038/s41588-021-00861-8DOI Listing
June 2021

A dual-target molecular mechanism of pyrethrum repellency against mosquitoes.

Nat Commun 2021 05 5;12(1):2553. Epub 2021 May 5.

Department of Entomology, Michigan State University, East Lansing, MI, USA.

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this study, we find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-β-farnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Thus, pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases.
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http://dx.doi.org/10.1038/s41467-021-22847-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099882PMC
May 2021

The N-terminal 5-68 amino acids domain of the minor capsid protein VP1 of human parvovirus B19 enters human erythroid progenitors and inhibits B19 infection.

J Virol 2021 May 5. Epub 2021 May 5.

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA

Parvovirus B19 (B19V) infection causes diseases in humans ranging from the mild to severe hematological disorders. The unique region of the minor structural protein VP1 (VP1u) of 227 amino acids harbors strong neutralizing epitopes which elicit dominant immune responses in patients. Recent studies have shown that the VP1u selectively binds to and enters B19V permissive cells through an unknown cellular proteinaceous receptor. In the present study, we demonstrated that purified recombinant VP1u effectively inhibits B19V infection of expanded primary human erythroid progenitors. Furthermore, we identified the amino acid sequence 5-68 of the VP1 (VP1u) is sufficient to confer the inhibition of B19V infection at a level similar to that of the full-length VP1u. structure prediction suggests that the VP1u contains three α-helices. Importantly, we found that the inhibition capability of the minimal domain VP1u is independent of its dimerization but is likely dependent on the structure of the three predicated α-helices. As VP1u outcompetes the full-length VP1u in entering cells, we believe that VP1u functions as a receptor-binding ligand during virus entry. Finally, we determined the effective inhibition potency of VP1u in B19V infection of human erythroid progenitors, which has a half maximal effective concentration (EC) of 67 nM, suggesting an anti-viral peptide candidate to combat B19V infection.Human parvovirus B19 infection causes severe hematological disorders, including transient aplastic crisis, pure red cell aplasia, and hydrops fetalis. A productive B19 infection is highly restricted to human erythroid progenitors in human bone marrow and fetal liver. In the current study, we identified that the N-terminal 5-68 amino acids domain of the minor viral capsid protein VP1 enters expanded human erythroid progenitors, which is nearly 5 times more efficient than the full-length VP1 unique region (1-227aa). Importantly, purified recombinant 5-68aa of the VP1 has a high efficiency in inhibition of parvovirus B19 infection of human erythroid progenitors, which has a half maximal effective concentration (EC) of 67 nM and a low cytotoxicity. The N-terminal 5-68 amino acids holds the potential as an effective antiviral of parvovirus B19 caused hematological disorders, as well as a carrier to deliver proteins to human erythroid progenitors.
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http://dx.doi.org/10.1128/JVI.00466-21DOI Listing
May 2021

Population genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii.

Nat Commun 2021 05 3;12(1):2491. Epub 2021 May 3.

Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.
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http://dx.doi.org/10.1038/s41467-021-22760-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093194PMC
May 2021

Dual effects of quercetin on protein digestion and absorption in the digestive tract.

Food Chem 2021 Oct 20;358:129891. Epub 2021 Apr 20.

College of Chemistry, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, Fuzhou University, Fuzhou, China; College of Biological Science and Engineering, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, Fuzhou University, Fuzhou, China; Fujian Key Laboratory of Marine Enzyme Engineering, Fuzhou University, Fuzhou, China. Electronic address:

Quercetin is a well-studied natural product with multiple pharmacological properties. In this study, we demonstrated that quercetin suppressed protein digestion in the intestinal fluid by inhibiting trypsin, a key digestive enzyme. However, we also observed a previously unknown property of quercetin: promoting the intestinal absorption of proteins. In addition, the promoted protein absorption was mediated by internalization of digested oligopeptides in the intestinal epithelia rather than increasing the intestinal paracellular permeability. Notably, four other flavonoids also achieved such enhanced intestinal absorption, suggesting that this effect was associated with the aglycone flavonol backbone, but not related to their inhibitory potencies against trypsin. This study demonstrates that quercetin exhibits dual effects on protein digestion and absorption: 1) suppressing protein digestion by inhibiting trypsin in the intestinal fluid; 2) promoting the intestinal absorption of oligopeptides in the intestinal villi cells.
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http://dx.doi.org/10.1016/j.foodchem.2021.129891DOI Listing
October 2021