Publications by authors named "Yanyan Wang"

605 Publications

Diagnostic value of miR-153 and miR-203 in patients with cervical cancer and their correlation with human papillomavirus infection.

Am J Transl Res 2021 15;13(8):9736-9742. Epub 2021 Aug 15.

Department of Obstetrics and Gynecology, Huzhou Central Hospital Huzhou, Zhejiang Province, China.

Objective: To explore the diagnostic value of miR-153 and miR-203 in patients with cervical cancer (CC).

Methods: A total of 136 CC and suspected CC patients admitted to our hospital were enrolled in this prospective study. Among them, 80 cases had CC, 56 cases with cervical intraepithelial neoplasia, and 40 cases with cervicitis. The normal cervical tissues of the above 176 patients were taken as a control and the expression levels of miR-153, miR-203 and human papillomavirus (HPV) DNA in CC tissues were detected.

Results: The relative expressions of miR-153 and miR-203 in the CC group were significantly lower than those in the cervicitis and cervical intraepithelial neoplasia groups (all P<0.01). The area under the ROC curve of miR-153 for the diagnosis of CC was 0.883 (95% CI: 0.828-0.938, P<0.001). When the cut-off value of miR-153 expression level in the diagnosis of CC was 0.27, its Youden index, specificity, and sensitivity were 0.748, 0.863, and 0.885, respectively. The area under the ROC curve of miR-203 for the diagnosis of CC was 0.752 (95% CI: 0.680-0.825, P<0.001). When the cut-off value of miR-203 expression level in the diagnosis of CC was 0.51, its Youden index, specificity, and sensitivity were 0.478, 0.615, and 0.863, respectively. Compared with the cervical intraepithelial neoplasia group, HPV infection rate in the CC group was significantly higher (P<0.001). The relative expression levels of miR-153 and miR-203 in HPV-positive patients were significantly lower than those in HPV-negative patients (P<0.001). Significantly lower levels of miR-153 and miR-203 were found in patients with myometrial infiltration, FIGO III-IV stage, and lymphatic metastasis (P<0.05).

Conclusion: The expressions of miR-152 and miR-203 are down-regulated in patients with CC, which has diagnostic value for CC. The expressions of miR-153 and miR-203 are correlated with HPV infection and aggressiveness of tumor.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430153PMC
August 2021

The Prevalence, Risk Factors and Clinical Correlates of QTc Prolongation in Chinese Hospitalized Patients With Chronic Schizophrenia.

Front Psychiatry 2021 16;12:704045. Epub 2021 Aug 16.

Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China.

The QTc interval may be significantly prolonged in schizophrenia patients taking antipsychotics. Few studies have addressed QTc prolongation (QTP) in Chinese patients. This study was designed to evaluate the prevalence of QTP and its clinical correlates in Chinese hospitalized patients with chronic schizophrenia. A total of 436 inpatients and 291 normal controls matched with age and sex were included. QTc prolongation was defined as 2 standard deviations (SD) above the mean value of normal controls. Positive and Negative Syndrome Scale (PANSS) and its five-factor model were used to evaluate psychopathological symptoms. QTc interval was significantly longer in patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. More women than men displayed QTP. Compared with patients without QTP, the patients with QTP had significantly higher concrete/disorganized subscore, lower low density lipoprotein (LDL) and lower total protein (TP). Furthermore, binary logistic regression analysis showed that higher number of hospitalizations, higher concrete/disorganized subscore and lower LDL were risk factors for QTP. Correlation analysis indicated significant association between QTc interval and the following variables: sex, age, duration of illness, the number of hospitalizations, PANSS total score, fasting blood glucose (FPG). Finally, a multiple regression analysis showed that older age, antipsychotic polypharmacy, higher PANSS total score, and lower LDL were risk factors for QTP. Among them, LDL seemed to be a protective factor for QTP. QTc interval was longer in schizophrenia patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. Some clinical characteristics were risk factors for QTP. And LDL seemed to be a protective factor for QTP.
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http://dx.doi.org/10.3389/fpsyt.2021.704045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416174PMC
August 2021

Probabilistic Risk Assessment of Dietary Exposure to Chloramphenicol in Guangzhou, China.

Int J Environ Res Public Health 2021 08 20;18(16). Epub 2021 Aug 20.

Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China.

Chloramphenicol has been used in veterinary medicine, where its residues can remain in food of animal origin, thus potentially causing adverse health effects. This facilitated the ban for its use in food-producing animals globally, but its residues have remained ubiquitous. In this study, food commodities possibly contaminated with chloramphenicol, including livestock meat, poultry, edible viscera, fish, shrimp and crab, molluscs, milk, and eggs, were collected from domestic retail shops in all the 11 districts of Guangzhou and tested for its residue. Probabilistic risk assessment model calculations for its dietary exposure, and the margin of exposure (displayed as mean values and 5th percentile to 95th percentile ranges) were performed by using @RISK software based on a Monte Carlo simulation with 10,000 iterations. The results indicated the detection of chloramphenicol in 248 out of 1454 samples (17.1%), which averaged to a level of 29.1 μg/kg. The highest average value was observed in molluscs (148.2 μg/kg, with the top value as 8196 μg/kg); meanwhile, based on the dietary structure of a typical Cantonese, pond fish, pork, and poultry meat contributed most (about 80%) to the residents' dietary exposure to chloramphenicol. The margin of exposure for dietary chloramphenicol exposure in Guangzhou residents was 2489, which was apparently below 5000 (the borderline for judging a health risk), particularly low in preschool children (2094, suggesting an increased risk). In conclusion, the study suggests that chloramphenicol exposure in Guangzhou residents is considerable, and its relevant health hazard, especially for preschool children, is worthy of further investigation.
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http://dx.doi.org/10.3390/ijerph18168805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391991PMC
August 2021

Flexible Wireless Passive LC Pressure Sensor with Design Methodology and Cost-Effective Preparation.

Micromachines (Basel) 2021 Aug 18;12(8). Epub 2021 Aug 18.

Shenzhen Institute for Advanced Study, University of Electronics Science and Technology of China, Shenzhen 518110, China.

Continuous monitoring of physical motion, which can be successfully achieved via a wireless flexible wearable electronic device, is essential for people to ensure the appropriate level of exercise. Currently, most of the flexible LC pressure sensors have low sensitivity because of the high Young's modulus of the dielectric properties (such as PDMS) and the inflexible polymer films (as the substrate of the sensors), which don't have excellent stretchability to conform to arbitrarily curved and moving surfaces such as joints. In the LC sensing system, the metal rings, as the traditional readout device, are difficult to meet the needs of the portable readout device for the integrated and planar readout antenna. In order to improve the pressure sensitivity of the sensor, the Ecoflex microcolumn used as the dielectric of the capacitive pressure sensor was prepared by using a metal mold copying method. The Ecoflex elastomer substrates enhanced the levels of conformability, which offered improved capabilities to establish intimate contact with the curved and moving surfaces of the skin. The pressure was applied to the sensor by weights, and the resonance frequency curves of the sensor under different pressures were obtained by the readout device connected to the vector network analyzer. The experimental results show that resonant frequency decreases linearly with the increase of applied pressure in a range of 0-23,760 Pa with a high sensitivity of -2.2 MHz/KPa. We designed a coplanar waveguide-fed monopole antenna used to read the information of the LC sensor, which has the potential to be integrated with RF signal processing circuits as a portable readout device and a higher vertical readout distance (up to 4 cm) than the copper ring. The flexible LC pressure sensor can be attached to the skin conformally and is sensitive to limb bending and facial muscle movements. Therefore, it has the potential to be integrated as a body sensor network that can be used to monitor physical motion.
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http://dx.doi.org/10.3390/mi12080976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399622PMC
August 2021

Network-based approach to identify prognosis-related genes in tamoxifen-treated patients with estrogen receptor-positive breast cancer.

Biosci Rep 2021 Sep;41(9)

Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China.

Tamoxifen is an estrogen receptor (ER) antagonist that is most commonly used for the treatment of ER-positive breast cancer. However, tamoxifen resistance remains a major cause of cancer recurrence and progression. Here, we aimed to identify hub genes implicated in the progression and prognosis of ER-positive breast cancer following tamoxifen treatment. Microarray data (GSE9893) for 155 tamoxifen-treated primary ER-positive breast cancer samples were obtained from the Gene Expression Omnibus database. In total, 1706 differentially expressed genes (DEGs), including 859 up-regulated and 847 down-regulated genes, were identified between relapse and relapse-free samples. Weighted correlation network analysis clustered genes into 13 modules, among which the tan and blue modules were the most significantly related to prognosis. From these two modules, we further identified and validated two prognosis-related hub genes (G-rich RNA sequence binding factor 1 (GRSF1) and microtubule-associated protein τ (MAPT)) via survival analysis based on several publicly available datasets. High expression of GRSF1 predicted poor prognosis, whereas MAPT indicated favorable outcomes in ER-positive breast cancer. Using breast cancer cell lines and tissue samples, we confirmed that GRSF1 was significantly up-regulated and MAPT was down-regulated in the tamoxifen-resistant group compared with the tamoxifen-sensitive group. The prognostic value of GRSF1 and MAPT was also verified in 48 tamoxifen-treated ER-positive breast cancer patients in our hospital. Gene set enrichment analysis (GSEA) suggested that GRSF1 was potentially involved in RNA degradation and cell cycle pathways, while MAPT was strongly linked to immune-related signaling pathways. Taken together, our findings established novel prognostic biomarkers to predict tamoxifen sensitivity, which may facilitate individualized management of breast cancer.
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http://dx.doi.org/10.1042/BSR20203020DOI Listing
September 2021

Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients.

Front Med (Lausanne) 2021 19;8:690100. Epub 2021 Jul 19.

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Recent studies on follicular regulatory T (Tfr) and follicular helper T (Tfh) cells suggest that they may participate in the pathogenesis of rheumatoid arthritis (RA). Here, we examine Tfr-like and Tfh-like cells and their subsets in RA and assess the correlations between these subsets with B cells and cytokines related to the pathogenesis of RA and their clinical significance. The study population consisted of 18 healthy controls and 47 RA patients (17 new onset, 57.00 ± 11.73 years; 30 treated RA patients, 57.56 ± 1.97 years). Disease activity scores in 28 joints were calculated. The positive rates of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) were 82.9 and 89.4%, respectively. Cell subsets were analyzed using flow cytometry, and serum cytokine levels were measured using cytometric bead array. Tfh-like and PD-1 Tfh-like cells were elevated, and the distribution of Tfh-like cell subsets was altered with increased Tfh17-like and Tfh1/17-like cells in RA patients. The receiver operating characteristics curves for Tfh-like, Tfh17-like, Tfh1/17-like, and PD-1 Tfh-like cells indicate improved RA diagnostic potential. RA patients had decreased regulatory T (Treg), Tfr-like, and memory Tfr-like (mTfr-like) cells and increased Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios. Tfh-like cells and their subsets, including Tfh1-like, Tfh2-like, Tfh1/17-like, and PD-1 Tfh-like cells, were positively correlated with B cells. Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios were positively correlated with B cells in new-onset RA. Interleukin (IL)-2, IL-4, IL-17, interferon-γ, and tumor necrosis factor-α were positively correlated with Tfr-like and mTfr-like cells. IL-2 and IL-10 were positively correlated with Tfh-like and Tfh2-like cells. IL-4 was positively correlated with Tfh-like cells. Tfh-like and PD-1 Tfh-like cells are increased, whereas Treg, Tfr-like, and mTfr-like cells are decreased in RA, leading to an imbalance in Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios. Tfh-like cells and a portion of their subsets as well as Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios are closely related to B cells. Dysfunction of cell subsets leads to abnormal levels of cytokines involved in the pathogenesis of RA. The altered distributions of Tfh-like cell subsets, especially Tfh1/17-like cells, represent potential therapeutic targets for treatment of RA.
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http://dx.doi.org/10.3389/fmed.2021.690100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326448PMC
July 2021

New Insights From Single-Cell Sequencing Data: Synovial Fibroblasts and Synovial Macrophages in Rheumatoid Arthritis.

Front Immunol 2021 19;12:709178. Epub 2021 Jul 19.

Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

Single-cell RNA sequencing (scRNA-seq) technology can analyze the transcriptome expression level of cells with high-throughput from the single cell level, fully show the heterogeneity of cells, and provide a new way for the study of multicellular biological heterogeneity. Synovitis is the pathological basis of rheumatoid arthritis (RA). Synovial fibroblasts (SFs) and synovial macrophages are the core target cells of RA, which results in the destruction of articular cartilage, as well as bone. Recent scRNA-seq technology has made breakthroughs in the differentiation and development of two types of synovial cells, identification of subsets, functional analysis, and new therapeutic targets, which will bring remarkable changes in RA treatment.
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http://dx.doi.org/10.3389/fimmu.2021.709178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326910PMC
July 2021

Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization.

Biomater Sci 2021 Sep 14;9(18):6153-6168. Epub 2021 Sep 14.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, P. R. China.

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into the anti-inflammatory phenotype (M2) for atherosclerosis regression. These might be realized simultaneously by drug-loaded discoidal reconstituted high-density lipoproteins (d-rHDLs) with the functions of cellular cholesterol efflux and targeted drug delivery on macrophages. However, cholesterol reception can drive the remodelling of d-rHDLs, which serves to release drugs specifically in the atherosclerotic plaque but might incur premature drug leakage in blood circulation. Given that, the proposed strategy is to inhibit the remodelling behaviour of the carrier in blood circulation and responsively accelerate it under the atherosclerotic microenvironmental stimulus. Herein, atorvastatin calcium-loaded d-rHDL was modified by a PEGylated ferrocene/β-cyclodextrin supramolecular copolymer (PF/TC) to construct ROS-responsive PF/TC-AT-d-rHDL, which is expected to possess plasma stability and biosafety as well as triggered drug release by cholesterol efflux promotion. As a result, PF/TC-AT-d-rHDL could responsively dissemble into β-cyclodextrin modified AT-d-rHDL under the ROS-triggered dissociation of PF/TC, therefore exhibiting increased cholesterol efflux from the cholesterol donor and drug release through the remodelling behaviour of the carrier . Moreover, PF/TC-AT-d-rHDL enhanced cellular cholesterol removal in foam cells after response to ROS, inhibiting intracellular lipid deposition compared with other d-rHDL carriers. Interestingly, cellular drug uptake was significantly promoted upon cellular cholesterol removal by restoring the permeability and fluidity of foam cell membranes as indicated by flow cytometry and fluorescence polarization analysis, respectively. Importantly, compared with untreated foam cells, PF/TC-AT-d-rHDL obviously increased the ratio of M2/M1 by 6.3-fold, which was even higher than the effect of PF/TC-d-rHDL (3.4-fold) and free drugs (1.9-fold), revealing that PF/TC-AT-d-rHDL synergistically promoted the M2 polarization of macrophages. Accordingly, PF/TC-AT-d-rHDL boosted the secretion of anti-inflammatory cytokines and inhibited that of inflammatory cytokines. Collectively, PF/TC-AT-d-rHDL exerted synergistic M2 polarization effects on foam cells for atherosclerotic immunomodulatory therapy responsively mediating cholesterol efflux and delivering drugs.
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http://dx.doi.org/10.1039/d1bm00610jDOI Listing
September 2021

Influence of cosmetic hair treatments on hair of methamphetamine abuser: Bleaching, perming and coloring.

Ecotoxicol Environ Saf 2021 Oct 23;222:112542. Epub 2021 Jul 23.

Beijing Municipal Public Security Bureau Judicial Appraisal Center, China.

Various cosmetic hair manipulations are known to interfere with the drug of abuse concentrations in hair. It is important to know the effects of cosmetic hair treatments as they may cause false-positive or false-negative results. The article aimed to investigate the effect of bleaching, perming, and dyeing treatment on the hair of methamphetamine(MA)abusers. The research results show that during the bleaching treatment, the content of MA in the hair is positively correlated with the degree of the treatment. Bleaching caused strong chemical degradation on MA, while perming exerted more a leaching out effect. Temporary dyes in single applications had only little effects on MA, Semi-permanent dyes can penetrate into the hair and exert a stronger matrix effect. The effect of permanent hair dye on the content of MA in hair mainly depends on the concentration of hydrogen peroxide.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112542DOI Listing
October 2021

The predictive value of microRNA in early hypertensive disorder complicating pregnancy (HDCP).

Am J Transl Res 2021 15;13(6):7288-7293. Epub 2021 Jun 15.

Obstetrics Department III, Cangzhou Central Hospital Cangzhou, China.

Objective: To examine the predictive value of microRNA (miRNA) in hypertensive disorder complicating pregnancy (HDCP).

Methods: 102 pregnant women with HDCP admitted to our hospital from March 2017 to June 2019 were recruited as the study cohort and randomly divided into an HDCP group, a mild preeclampsia group, and a severe preeclampsia group, with 34 patients in each group. In addition, 34 healthy pregnant women who underwent pregnancy tests in our hospital were recruited as the normal group. The relative expressions of plasma miR-19a, miR-126, and miRNA-210 in were measured. A Pearson correlation analysis was used to analyze the correlations between the miR-19a, miR-181b, and miRNA-210 expressions and the severity of HDCP. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of the miR-19a, miR-126, and miRNA-210 expressions.

Results: The miR-19a and miRNA-210 expressions were higher in the HDCP group, the mild preeclampsia group, and the severe preeclampsia group than they were in the normal group, and the miR-126 expression was lower (all P<0.05). The miR-19a, miR-126, and miRNA-210 expressions were different among the four groups (P<0.05). The miR-19a and miRNA-210 expression levels in the severe preeclampsia group were higher than they were in the HDCP group, and the miR-126 expression was lower (P<0.05). A Pearson correlation analysis showed the miR-19a and miR-210 levels in the HDCP patients were positively correlated with the severity of the disease (P<0.05), and the miR-126 level is negatively correlated with disease severity (P<0.05). Our ROC curve analysis demonstrated that the miR-19a, miR-126, and miR-210 levels have a predictive value for HDCP. The areas under the curve were 0.800, 0.633, and 0.723, the sensitivities were 81.2%, 71.4%, and 80.2%, and the specificities were 73.5%, 67.5%, 81.5%. Additionally, the area under the curve of the combination of the three was 0.896, and the sensitivity and specificity were 90.5% and 93.9% respectively.

Conclusion: miR-19a, miR-126, and miR-210 are strongly connected to the severity of HDCP and can be used as a sensitive indicator to predict HDCP patients clinically.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290685PMC
June 2021

The serum CK17 and CK19 expressions in cervical cancer patients and their prognostic value.

Am J Transl Res 2021 15;13(6):6439-6445. Epub 2021 Jun 15.

Department of Pathology, Zhejiang North Medical Center (Huzhou Central Hospital) Huzhou 313003, Zhejiang Province, China.

Objective: This study was designed to quantify the serum CK17 and CK19 expressions in cervical cancer (CC) patients and determine their predictive value.

Methods: A total of 124 CC patients admitted to Zhejiang North Medical Center (Huzhou Central Hospital) between November 2014 and November 2017 were recruited for the study and placed in a research group (the Res group), and 99 healthy individuals during the same period were also recruited for the study and placed in a control group (the Con group). Their serum CK17 and CK19 expressions were quantified, and the diagnostic significance of the two for CC was analyzed. Additionally, the patients were followed up for three years. The patients were then assigned to favorable and unfavorable prognosis groups, and then the predictive significance of CK17 and CK19 for such patients was evaluated.

Results: The Res group presented significantly higher serum CK17 and CK19 expression levels than the Con group, and the two factors were positively associated. Additionally, neither of the AUCs for serum CK17 and CK19 in identifying CC were less than 0.800, and the AUC of the combination of the two in identifying it was not smaller than 0.900. The AUC of the combination of serum CK17 and CK19 in identifying unfavorable CC prognoses was approximate 0.850, and high expression levels CK17 and CK19 were closely related with low three-year overall survival rates.

Conclusion: Serum CK17 combined with serum CK19 is of great diagnostic and predictive significance for CC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290704PMC
June 2021

CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis.

Cancer Cell Int 2021 Jul 19;21(1):384. Epub 2021 Jul 19.

Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Jianshe Dong Lu, Erqi District, Zhengzhou City, 450052, Henan Province, China.

Background: Circular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast cancer. Nevertheless, how and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast cancer.

Methods: Thirty nine paired breast cancer and normal tissues were harvested. circFBXL5, microRNA-216b (miR-216b) and high-mobility group AT-hook 2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, 5-FU resistance, migration, invasion, and apoptosis were tested via cell counting kit-8 assay, wound healing analysis, transwell analysis, and flow cytometry. The relationship of miR-216b and circFBXL5 or HMGA2 was tested via dual-luciferase reporter analysis and RNA pull-down assay. The impact of circFBXL5 on breast cancer tumor growth in vivo was analyzed via xenograft model.

Results: circFBXL5 was highly expressed in breast cancer tissues and cells, and was more upregulated in 5-FU-resistant breast cancer cells. Function experiments showed that circFBXL5 knockdown inhibited the 5-FU resistance of breast cancer by inhibiting cell migration, invasion and promoting apoptosis. In the terms of mechanism, miR-216b could be sponged by circFBXL5, and its inhibitor could also reverse the influence of circFBXL5 silencing on the 5-FU resistance of breast cancer cells. In addition, HMGA2 was a target of miR-216b, and its overexpression also reversed the regulation of miR-216b overexpression on the 5-FU resistance of breast cancer. Furthermore, circFBXL5 interference declined breast cancer tumor growth in xenograft model.

Conclusion: Our data showed that circFBXL5 could promote the 5-FU resistance of breast cancer by regulating miR-216b/HMGA2 axis.
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http://dx.doi.org/10.1186/s12935-021-02088-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287742PMC
July 2021

Constructing nitrided interfaces for stabilizing Li metal electrodes in liquid electrolytes.

Chem Sci 2021 Jul 1;12(26):8945-8966. Epub 2021 Jun 1.

Institute for Superconducting & Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong NSW 2522 Australia.

Traditional Li ion batteries based on intercalation-type anodes have been approaching their theoretical limitations in energy density. Replacing the traditional anode with metallic Li has been regarded as the ultimate strategy to develop next-generation high-energy-density Li batteries. Unfortunately, the practical application of Li metal batteries has been hindered by Li dendrite growth, unstable Li/electrolyte interfaces, and Li pulverization during battery cycling. Interfacial modification can effectively solve these challenges and nitrided interfaces stand out among other functional layers because of their impressive effects on regulating Li flux distribution, facilitating Li diffusion through the solid-electrolyte interphase, and passivating the active surface of Li metal electrodes. Although various designs for nitrided interfaces have been put forward in the last few years, there is no paper that specialized in reviewing these advances and discussing prospects. In consideration of this, we make a systematic summary and give our comments based on our understanding. In addition, a comprehensive perspective on the future development of nitrided interfaces and rational Li/electrolyte interface design for Li metal electrodes is included.
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http://dx.doi.org/10.1039/d1sc01806jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261733PMC
July 2021

Expression of antibody fragments in Saccharomyces cerevisiae strains evolved for enhanced protein secretion.

Microb Cell Fact 2021 Jul 14;20(1):134. Epub 2021 Jul 14.

Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.

Monoclonal antibodies, antibody fragments and fusion proteins derived thereof have revolutionized the practice of medicine. Major challenges faced by the biopharmaceutical industry are however high production costs, long processing times and low productivities associated with their production in mammalian cell lines. The yeast Saccharomyces cerevisiae, a well-characterized eukaryotic cell factory possessing the capacity of post-translational modifications, has been industrially exploited as a secretion host for production of a range of products, including pharmaceuticals. However, due to the incompatible surface glycosylation, few antibody molecules have been functionally expressed in S. cerevisiae. Here, three non-glycosylated antibody fragments from human and the Camelidae family were chosen for expression in a S. cerevisiae strain (HA) previously evolved for high α-amylase secretion. These included the Fab fragment Ranibizumab (Ran), the scFv peptide Pexelizumab (Pex), and a nanobody consisting of a single V-type domain (Nan). Both secretion and biological activities of the antibody fragments were confirmed. In addition, the secretion level of each protein was compared in the wild type (LA) and two evolved strains (HA and MA) with different secretory capacities. We found that the secretion of Ran and Nan was positively correlated with the strains' secretory capacity, while Pex was most efficiently secreted in the parental strain. To investigate the mechanisms for different secretion abilities in these selected yeast strains for the different antibody fragments, RNA-seq analysis was performed. The results showed that several bioprocesses were significantly enriched for differentially expressed genes when comparing the enriched terms between HA.Nan vs. LA.Nan and HA.Pex vs. LA.Pex, including amino acid metabolism, protein synthesis, cell cycle and others, which indicates that there are unique physiological needs for each antibody fragment secretion.
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http://dx.doi.org/10.1186/s12934-021-01624-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278646PMC
July 2021

Hepatic Branch Vagotomy Modulates the Gut-Liver-Brain Axis in Murine Cirrhosis.

Front Physiol 2021 25;12:702646. Epub 2021 Jun 25.

Division of Gastroenterology, Hepatology, and Nutrition, Central Virginia Veterans Health Care System, Virginia Commonwealth University, Richmond, VA, United States.

Background: Cirrhosis and hepatic encephalopathy (HE) are linked with an altered gut-liver-brain axis, however, the relative contribution of hepatic vagal innervation is unclear. We aimed to determine the impact of hepatic vagotomy on the gut microbiome, brain, and liver in murine cirrhosis.

Methods: 10-15-week-old male C57BL/6 mice with and without hepatic vagotomy underwent carbon tetrachloride (CCl4) gavage for 8 weeks. Frontal cortex [inflammation, glial/microglial activation, BDNF (brain-derived neurotrophic factor)], liver [histology including inflammation and steatosis, fatty acid synthesis (sterol-responsive binding protein-1) SREBP-1, insulin-induced gene-2 (Insig2) and BDNF], and colonic mucosal microbiota (16srRNA microbial sequencing) were evaluated on sacrifice. Conventional mice with and without cirrhosis were compared to vagotomized counterparts.

Results: : Cirrhosis resulted in dysbiosis, hepatic/neuro-inflammation with glial/microglial activation, and low brain BDNF vs. controls. Vagotomized control mice had a lower colonic dysbiosis than conventional mice but the rest of the hepatic/brain parameters were similar. After vagotomy + cirrhosis, we found lower dysbiosis but continuing neuroinflammation in the absence of glial/microglial activation vs. conventional cirrhosis. Vagotomy + Cirrhosis groups showed higher hepatic steatosis due to higher SREBP1 and low Insig2 protein and altered activation of key genes involved in hepatic lipid metabolism and inflammation. BDNF levels in the brain were higher but low in the liver in vagotomy + cirrhosis, likely a protective mechanism.

Conclusions: Hepatic vagal innervation affects the gut microbial composition, hepatic inflammation and steatosis, and cortical inflammation and BDNF expression and could be a critical modulator of the gut-liver-brain axis with consequences for HE development.
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http://dx.doi.org/10.3389/fphys.2021.702646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268007PMC
June 2021

An ultra-red fluorescent biosensor for highly sensitive and rapid detection of biliverdin.

Anal Chim Acta 2021 Aug 31;1174:338709. Epub 2021 May 31.

School of Life Sciences, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, College of Precision Instrument and Opto-electronics Engineering, Tianjin University, Tianjin, 300072, China; Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, 300457, China. Electronic address:

The important role of BV in clinical diagnostics of liver-related diseases has been established in veterinary medicine. However, the sensitivity and selectivity of the current BV assays remain relatively low compromising its wider application in clinical diagnosis. Herein, we developed a rapid and sensitive BV-detecting biosensor based on a novel far-red fluorescent protein smURFP, which produced fluorescence only through specific interaction with its cofactor BV. In our study, the binding of BV to smURFP was then systematically optimized based on the structures of the smURFP + BV complex to increase the sensitivity of our biosensor. A wide linear range from 0 μM to 25 μM was obtained in both chicken and human serum. The limit of detection (LOD) and limit of quantification (LOQ) for BV was as low as 0.4 nM and 1.5 nM in human serum, and 0.4 nM and 1.2 nM in chicken serum. To our knowledge, this is the lowest LOD that has ever been reported for a BV biosensor. Our study sheds light on the biological and clinical analysis of BV.
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http://dx.doi.org/10.1016/j.aca.2021.338709DOI Listing
August 2021

Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU).

Cell Death Dis 2021 07 9;12(7):690. Epub 2021 Jul 9.

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Emerging evidence has declared that Proteasome 26S subunit ATPase 2 (PSMC2) is involved in tumor progression. However, its role in breast cancer has not been investigated. Therefore, we sought to establish a correlation between breast cancer and PSMC2. PSMC2 expression in tissues was detected by immunohistochemistry. Loss-of-function study was used to evaluate the effects of PSMC2 knockdown in cell proliferation, apoptosis and migration. A gene microarray was performed to explore the potential downstream of PSMC2 with the help of Ingenuity Pathway Analysis (IPA). The effects of the PSMC2/PLAU axis on breast cancer were examined in vitro. Compared to para-cancer tissues, PSMC2 level was considerably elevated in breast cancer, which was significantly correlated with tumor grade. Knockdown of PSMC2 suppressed breast cancer progression in vitro and in vivo. The mechanistic research revealed that PSMC2 promotes the development and progression of human breast cancer through interacting with PLAU. Outcomes of our study showed that overexpression of PSMC2 provide tumorigenic and metastatic advantages in breast cancer, which may involve the regulation of PLAU. This study not only reveals a critical mechanism of breast cancer development, but also provides a promising therapeutic target for breast cancer treatment.
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http://dx.doi.org/10.1038/s41419-021-03960-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271021PMC
July 2021

Microbial Cell Factories for Green Production of Vitamins.

Front Bioeng Biotechnol 2021 17;9:661562. Epub 2021 Jun 17.

Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

Vitamins are a group of essential nutrients that are necessary to maintain normal metabolic activities and optimal health. There are wide applications of different vitamins in food, cosmetics, feed, medicine, and other areas. The increase in the global demand for vitamins has inspired great interest in novel production strategies. Chemical synthesis methods often require high temperatures or pressurized reactors and use non-renewable chemicals or toxic solvents that cause product safety concerns, pollution, and hazardous waste. Microbial cell factories for the production of vitamins are green and sustainable from both environmental and economic standpoints. In this review, we summarized the vitamins which can potentially be produced using microbial cell factories or are already being produced in commercial fermentation processes. They include water-soluble vitamins (vitamin B complex and vitamin C) as well as fat-soluble vitamins (vitamin A/D/E and vitamin K). Furthermore, metabolic engineering is discussed to provide a reference for the construction of microbial cell factories. We also highlight the current state and problems encountered in the fermentative production of vitamins.
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http://dx.doi.org/10.3389/fbioe.2021.661562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247775PMC
June 2021

Whether cranial expansion is indicated in selected cases with microcephaly?

Clin Neurol Neurosurg 2021 08 11;207:106748. Epub 2021 Jun 11.

Department of Paediatric Neurosurgery, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Luding Rd. 355, Shanghai, China. Electronic address:

Purpose: Some children with microcephaly experienced severe social emotional deficits during their 1-2 years of age. Cranial expansion is generally not used in these cases. Our aim is to assess whether such operation is effective to improve their social emotional status, and thereby boosting their functional development in selected cases with such condition.

Methods: A retrospective cohort review in microcephalic cases who had undergone cranial expansion in Shanghai Children's Hospital since Jun. 2016 to Jun. 2017 with at least 12 months follow-up was conducted. Inclusion and exclusion criteria were set for the selection of the target patients in the current study. Our study focused on the changes of social emotional status (evaluated by The Infant-Toddler Social and Emotional Assessment, ITSEA) and functional development (applying neurodevelopmental questionnaire) pre- and 12 months post-op in these cases.

Results: A total of 14 cases were included in the current study. On the basis of a 2-cm enlargement during surgery(1 cm advancement of fronto-orbital rim on each side), HC continued to increase at an average of 0.5 cm in one year after the procedure in these cases, making its corresponding standard deviation improve from -4.5 to -3.4. Among those 14 cases, 11 (78.6%) showed improvement in all of these four domains in ITSEA at 12 months post-op. Scores were significantly better at 12 months post-op with p < 0.01 compared with those in domains of internalizing behavior and dysregulation behavior pre-operatively. Improvement was observed with p < 0.05 in domains of externalizing behavior and social-emotional competence as well. With regard to functional development, 8 cases (57.1%) were revealed improvement in all of these three sections of motor, speech and cognitive function in the questionnaire, 5 (35.7%) concluded partially upgraded in 1 or 2 sections. Only one (7.1%) showed no change during the follow-up. No surgery-related complications were recorded in the current study.

Conclusion: When progressive copper-beaten sign is revealed in their serial skull X-rays, microcephalic cases with social emotional deficits in their 1-2 years of age could benefit from cranial expansion surgery with regard to improving their social emotional status and functional development.
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http://dx.doi.org/10.1016/j.clineuro.2021.106748DOI Listing
August 2021

Propofol Mediated Protection of the Brain From Ischemia/Reperfusion Injury Through the Regulation of Microglial Connexin 43.

Front Cell Dev Biol 2021 8;9:637233. Epub 2021 Jun 8.

Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Cerebral ischemia/reperfusion (I/R) injury is a serious condition that leads to increased apoptosis of microglial and neurons in the brain. In this study, we identified that Cx43 expression level is significantly increased in the microglial cells during I/R injury. Using an model (hypoxia/reoxygenation-H/R injury), we observed that H/R injury leads to an increase in activation of microglial cells and increase in levels of pro-inflammatory markers such as IL-1β, IL-6, and TNF-α. Additionally, we could also observe significant increase in phosphorylation of Cx43 and Cav3.2 levels. To assess the role of H/R injured microglial cells on neuronal population, we cultured the neurons with conditioned media (MCS) from H/R injured microglial cells. Interestingly, we observed that microglial H/R injury significantly decreased Map2 expression and affected neuronal morphology. Further, we aimed to assess the effects of propofol on cerebral H/R injury, and observed that 40 μM propofol significantly decreased Cx43, Cx43 phosphorylation, and CaV3.2 levels. Additionally, propofol decreased apoptosis and increased Map2 expression levels in H/R injured neurons. Using silencing experiments, we confirmed that siCx43 could significantly improve the propofol's rescue after H/R injury in both microglia and neurons. We further developed an MCAO (middle cerebral artery occlusion) rat model to understand the effect of propofol in I/R injury. Interestingly, propofol treatment and downregulation of Cx43 significantly decreased the infract volume and apoptosis in these MCAO rats. Thus, this study clearly establishes that propofol protects the brain against I/R injury through the downregulation of Cx43 in microglial cells.
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http://dx.doi.org/10.3389/fcell.2021.637233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217990PMC
June 2021

Randomised, Double-Blind, Placebo-Controlled Study of Iguratimod in the Treatment of Active Spondyloarthritis.

Front Med (Lausanne) 2021 2;8:678864. Epub 2021 Jun 2.

Department of Rheumatology and Immunology, First Medical Center, General Hospital of Chinese People's Liberation Army, Beijing, China.

The effect of Iguratimod in the treatment of rheumatoid arthritis was confirmed in past studies. In terms of the mechanism of the effect and clinical application experience, Iguratimod has a potential value in the treatment of spondyloarthritis (SpA). This study evaluated the efficacy and safety of Iguratimod on active SpA. Subjects with active SpA were enrolled and randomly divided into two groups at a ratio of 1:2 (placebo vs. Iguratimod). On the basis of non-steroidal anti-inflammatory drugs, combined treatment with Iguratimod or placebo, followed by follow-up every 4 weeks for 24 weeks. The primary efficacy endpoint was to evaluate the alleviation rate of ASAS20; the important improvement of ASDAS and the efficacy of spinal mobility, physical function and quality of life at the 24th week. A total of 48 cases in the Iguratimod group and 25 cases in the placebo group were included in the final analysis. On the 24th week, the percentage of responders to ASAS20 (80 vs. 44%) and ASAS40 (56 vs. 20%) treated with Iguratimod were significantly higher than that in the placebo group ( < 0.05). Twelve cases had gastrointestinal discomfort, of which eight were in the Iguratimod group (16.7%, one case withdrew from the study due to diarrhoea) and four were in the placebo group (16.0%). No significant difference was found between the two groups ( < 0.05). Three cases of elevated transaminase were observed in the Iguratimod group and none in the placebo group, with no significant difference ( < 0.05). Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good.
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http://dx.doi.org/10.3389/fmed.2021.678864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208078PMC
June 2021

The influential factors and intervention strategies that engage malignant cancer patients in health-promoting behaviors during PICC line maintenance.

Am J Transl Res 2021 15;13(5):5208-5215. Epub 2021 May 15.

Department of Breast and Thoracic Tumors Surgery, The First Affiliated Hospital of Hainan Medical University Haikou 570100, Hainan Province, China.

Objective: To analyze the influential factors and intervention strategies involved in engaging health-promoting behaviors (EHPD) during peripheral central venous catheter (PICC) line maintenance in malignant tumor patients.

Methods: 120 patients with malignant tumors who underwent PICC line maintenance in our hospital were prospectively analyzed. They were divided into a low and moderate level group (HPLP-II score ≤137) and a high level group (HPLP-II score >137) according to their Health Promoting Lifestyle Profile II (HPLP-II) questionnaire scores. Single-factor and multifactor analyses were performed to identify the factors influencing the patients' engagement in self-health-promoting behaviors. The one hundred and twenty patients with malignant tumors were randomly divided into two groups (n=60 in each group). The control group and the intervention group underwent routine nursing care and patient education. The two groups were compared in terms of the changes in their HPLP-II scores, their Cancer Patients PICC Self-management Scale (CPPSM) scores, their SAS and their SDS scores before and after the intervention, as well as their maintenance compliance rates, their complication rates during catheter placement, and their lack of PICC maintenance.

Results: Literacy, place of residence, duration of catheter use, self-management abilities of PICCs, social support, and anxiety were risk factors (>1, <0.05). Compared with their pre-intervention scores, the HPLP-II and CPPSM scores were increased in both groups (<0.05), and the SAS and SDS scores were decreased in both groups after the intervention (<0.05), and the intervention group had higher scores than the control group (<0.05). The intervention group exhibited a higher maintenance compliance rate than the control group (<0.05). The incidence of complications and the lack of PICC maintenance in the intervention group were lower than they were in the control group (<0.05).

Conclusion: The influential factors during PICC maintenance for EHPD in malignant cancer patients include literacy, place of residence, duration of PICC use, . Patient education can promote patients' EHPD and self-management abilities, relieve their anxiety and depression, reduce their complications, and improve their compliance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205709PMC
May 2021

Prognostic and Therapeutic Significance of BTN3A Proteins in Tumors.

J Cancer 2021 27;12(15):4505-4512. Epub 2021 May 27.

School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China.

The Butyrophilin 3A (BTN3A) family is a type I transmembrane protein belonging to the immunoglobulin (Ig) superfamily. The family contains three members: BTN3A1, BTN3A2 and BTN3A3, which share 95% homology in the extracellular domain. The expression of BTN3A family members is different in different types of tumors, which plays an important role in tumor prognosis. Among them, there are many studies on tumor immunity of BTN3A1, which shows that it is essential for the activation of Vγ9Vδ2 T cells, while BTN3A3 is expected to become a potential therapeutic target for breast cancer. Recent studies have shown that the BTN3A family is closely related to the occurrence and development of tumors. Now the BTN3A family has become one of the research hotspots and is expected to become new tumor prediction and treatment targets.
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http://dx.doi.org/10.7150/jca.57831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210570PMC
May 2021

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR.

PeerJ 2021 25;9:e11429. Epub 2021 May 25.

Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China.

Background: Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells.

Methods: The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and sensitive K562 cells were established by RNA sequencing (RNA-seq). Expression of differentially expressed lncRNAs (DElncRNAs) and DEmRNAs was validated by qRT-PCR. The potential biological functions of DElncRNAs targets were identified by GO and KEGG pathway enrichment analyses, and the lncRNA-miRNA-mRNA ceRNA network was further constructed. K562/ADR cells were transfected with CCDC26 and LINC01515 siRNAs to detect the mRNA levels of GLRX5 and DICER1, respectively. The cell survival rate after transfection was detected by CCK-8 assay.

Results: The ceRNA network was composed of 409 lncRNA-miRNA pairs and 306 miRNA-mRNA pairs based on 67 DElncRNAs, 58 DEmiRNAs and 192 DEmRNAs. Knockdown of CCDC26 and LINC01515 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the half-maximal inhibitory concentration (IC) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC of doxorubicin.

Conclusions: The ceRNA regulatory networks may play important roles in drug resistance of leukemia cells. CCDC26/miR-140-5p/GLRX5 and LINC01515/miR-425-5p/DICER1 may be potential targets for drug resistance in K562/ADR cells. This study provides a promising strategy to overcome drug resistance and deepens the understanding of the ceRNA regulatory mechanism related to drug resistance in CML cells.
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http://dx.doi.org/10.7717/peerj.11429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162247PMC
May 2021

Comparative Analysis of Clinical and Imaging Features of Osteomalacia and Spondyloarthritis.

Front Med (Lausanne) 2021 20;8:680598. Epub 2021 May 20.

Department of Rheumatology and Immunology, The First Medical Center of PLA General Hospital, Beijing, China.

To compare the clinical and radiological characteristics of osteomalacia and spondyloarthritis/ankylosing spondylitis (SpA/AS) in order to provide a basis for differential diagnosis. We carried out a retrospective analysis of patients who were diagnosed with osteomalacia at the First Medical Center of 301 Hospital (Beijing, China) from January 2012 to January 2019. The clinical and radiological data of all patients were collected; at the same time, we selected age- and gender-matched patients with SpA/AS for comparison. We enrolled a total of 76 patients, 38 with osteomalacia, and 38 with SpA/AS. The mean ages of the two groups were, respectively 44.62 ± 14.90 years and 44.85 ± 9.76 years ( > 0.05). Of patients with osteomalacia, 65.79% ( = 25) had previously been misdiagnosed with SpA/AS. In the osteomalacia and SpA/AS groups, there were, respectively 31 and 33 patients with low back pain, 22 and 13 patients with peripheral arthralgia, and 13 and 3 patients with heel pain. Alkaline phosphatase (ALP) level was significantly higher in the osteomalacia than in the SpA/AS group ( < 0.05). Serum phosphorus levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and bone mineral density (BMD) were significantly lower in the osteomalacia group than the SpA/AS group ( < 0.05). Twenty-five patients in the osteomalacia group underwent sacroiliac-joint magnetic-resonance imaging (SIJ-MRI); abnormalities were found in 10 of these patients, seven of whom met the definition for positive SIJ-MRI according to 2009 Assessment of SpondyloArthritis international Society (ASAS) criteria. All seven presented with bilateral sacral involvement. Logistic-regression analysis found that the odds ratio (OR) for bone erosion score was 0.551; the higher this score, the lower the possibility of osteomalacia. Clinical and radiological presentations of patients with osteomalacia could highly simulate those of patients with spondyloarthritis; identifying the differences between these two diseases could effectively decrease the misdiagnosis rate.
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http://dx.doi.org/10.3389/fmed.2021.680598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172786PMC
May 2021

Regulatory Role of N6-methyladenosine (mA) Modification in Osteosarcoma.

Front Oncol 2021 19;11:683768. Epub 2021 May 19.

Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Osteosarcoma is the most common primary bone malignancy, typically occurring in childhood or adolescence. Unfortunately, the clinical outcomes of patients with osteosarcoma are usually poor because of the aggressive nature of this disease and few treatment advances in the past four decades. N6-methyladenosine (mA) is one of the most extensive forms of RNA modification in eukaryotes found both in coding and non-coding RNAs. Accumulating evidence suggests that mA-related factors are dysregulated in multiple osteosarcoma processes. In this review, we highlight mA modification implicated in osteosarcoma, describing its pathophysiological role and molecular mechanism, as well as future research trends and potential clinical application in osteosarcoma.
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http://dx.doi.org/10.3389/fonc.2021.683768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170137PMC
May 2021

The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues.

Biochem Biophys Res Commun 2021 Aug 2;565:29-35. Epub 2021 Jun 2.

State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China; Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. Electronic address:

Microtubule-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.65 Å). In addition, we summarized all of the previously published high-resolution crystal structures of ligands in the vinca site to provide structural insights for the rational design of the new vinca-site ligands. Moreover, based on the aligned results of the vinca site ligands, we provided three possible routes for designing new tubulysin analogues, namely macrocyclization between the N-14 side chain and the N-9 side chain, the hybird of tubulysin M and phomopsin A, and growing new aryl group at C-21. These designed structures will inspire the development of new MTAs or payloads in cancer therapy.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.086DOI Listing
August 2021

[Advances in metabolic engineering for vitamins production].

Sheng Wu Gong Cheng Xue Bao 2021 May;37(5):1748-1770

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

Vitamins are organic substances that are essential for the maintenance of life activities. Generally, vitamins need to be obtained from the diet or from some synthetic source as the body cannot synthesize vitamins, or the amounts of the synthesized vitamins are insufficient. At present, vitamins are widely used in medicine, food additives, feed additives, cosmetics and other fields, and the global demand for vitamins is constantly growing. Vitamins can be produced from chemical or microbial synthesis. Chemical synthesis usually requires harsh reaction conditions, produces serious wastes, and creates great potential safety hazard. In contrast, microbial synthesis of vitamins is greener, safer, and requires much less energy input. This review summarizes the advances in metabolic engineering for vitamins production in the past 30 years, with a focus on production of water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B7, B9, B12 and vitamin C precursors) and lipid-soluble vitamins (vitamin A, precursors of vitamin D, vitamin E and vitamin K). Moreover, the bottlenecks for fermentative production of vitamins are discussed, and future perspectives for developing next generation vitamins producing strains using synthetic biotechnology are prospected.
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http://dx.doi.org/10.13345/j.cjb.200696DOI Listing
May 2021

The P300/XBP1s/Herpud1 axis promotes macrophage M2 polarization and the development of choroidal neovascularization.

J Cell Mol Med 2021 Jul 31;25(14):6709-6720. Epub 2021 May 31.

Department of Ophthalmology, Ningbo Eye Hospital, Ningbo, China.

Neovascular age-related macular degeneration (AMD), which is characterized by choroidal neovascularization (CNV), leads to vision loss. M2 macrophages produce vascular endothelial growth factor (VEGF), which aggravates CNV formation. The histone acetyltransferase p300 enhances the stability of spliced X-box binding protein 1 (XBP1s) and promotes the transcriptional activity of the XBP1s target gene homocysteine inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (Herpud1). Herpud1 promotes the M2 polarization of macrophages. This study aimed to explore the roles of the p300/XBP1s/Herpud1 axis in the polarization of macrophages and the pathogenesis of CNV. Hypoxia-induced p300 interacted with XBP1s to acetylate XBP1s in RAW264.7 cells. Additionally, hypoxia-induced p300 enhanced the XBP-1s-mediated unfolded protein response (UPR), alleviated the proteasome-dependent degradation of XBP1s and enhanced the transcriptional activity of XBP1s for Herpud1. The hypoxia-induced p300/XBP1s/Herpud1 axis facilitated RAW264.7 cell M2 polarization. Knockdown of the p300/XBP1s/Herpud1 axis in RAW264.7 cells inhibited the proliferation, migration and tube formation of mouse choroidal endothelial cells (MCECs). The p300/XBP1s/Herpud1 axis increased in infiltrating M2-type macrophages in mouse laser-induced CNV lesions. Blockade of the p300/XBP1s/Herpud1 axis inhibited macrophage M2 polarization and alleviated CNV lesions. Our study demonstrated that the p300/XBP1s/Herpud1 axis in infiltrating macrophages increased the M2 polarization of macrophages and the development of CNV.
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http://dx.doi.org/10.1111/jcmm.16673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278076PMC
July 2021

Performance and responses of aerobic granular sludge at different concentrations of graphene oxide after a single administered dose.

Water Environ Res 2021 May 26. Epub 2021 May 26.

School of Environmental Science and Engineering, Qingdao University, Qingdao, China.

To investigate the impact of graphene oxide (GO) under different concentrations (0, 50, 100, 150, and 200 mg/L) on aerobic granular sludge (AGS) after a single administered dose, the performance of nitrogen removal, microbial enzymatic activity, extracellular polymeric substances (EPSs), and microbial community structure was analyzed in batch tests. The results showed that the impact of GO concentrations on AGS was dose- and time-dependent. Short-term GO exposure could accelerate the nitrification process of AGS, while relatively concentrations (≥100 mg/L) inhibited the process when present for extended periods of time. The microbial enzymatic activity showed similar tendency. The production of lactate dehydrogenase release (LDH) in 200 mg/L group was increased 48.04% and EPS contents decreased 30.06% compared to the control group at 30th day and showed that high concentrations of GO have toxic effects on AGS. The microbial bacteria responded differently to the stimulation of different concentrations of GO. PRACTITIONER POINTS: GO affected AGS system performance in concentration- and time-dependent manners. The nitrification rate of AGS increased in the short term and reversed over time. Long-term exposure to high GO concentrations caused toxicity to AGS. Different microorganisms had diverse responses to GO concentrations.
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http://dx.doi.org/10.1002/wer.1593DOI Listing
May 2021
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