Publications by authors named "Yali Wang"

490 Publications

MiR-222 regulates the progression of oral squamous cell carcinoma by targeting CDKN1B.

Am J Transl Res 2022 15;14(7):5215-5227. Epub 2022 Jul 15.

Department of Endodontics, Hu'nan Xiangya Stomatological Hospital, Central South University Changsha 410000, Hu'nan Province, China.

Objective: The purpose of this study was to establish a causal relationship between microRNA (miR-222) and oral squamous cell carcinoma (OSCC).

Methods: The cell viability of each treatment group was measured by MTT. The effects of miR-222 on cell metastasis and apoptosis were measured by transwell and flow cytometry. The targeting relationship between miR-222 and CDKN1B was verified by dual-luciferase reporter gene assay and Western blot. Cell derived xenograft was further constructed to verify the effect of miR-222 on tumor growth by observing tumor weight and volume. The proliferation of tumor tissue was determined by hematoxylin-eosin staining and immunohistochemical staining.

Results: Compared with those in adjacent tissues and normal cells, the levels of miR-222 in OSCC tissues and cells were significantly increased (P<0.05). The miR-222 mimic group promoted tumor cell proliferation, migration and cell cycle and inhibited cell apoptosis significantly (P<0.05). The up-regulation of CDKN1B expression inhibited cell viability, migration and invasiveness and promoted the apoptosis of OSCC (P<0.05). The dual-luciferase reporter gene assay found that miR-222 was targeted to CDKN1B and could inhibit fluorescence activity (P<0.05). assays showed that miR-222 could promote tumor growth through CDKN1B (P<0.05).

Conclusion: MiR-222 was significantly upregulated in OSCC tissues and cells and regulated tumor progression by targeting CDKN1B.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360895PMC
July 2022

Unraveling the contribution of pre-salting duration to microbial succession and changes of volatile and non-volatile organic compounds in Suancai (a Chinese traditional fermented vegetable) during fermentation.

Food Res Int 2022 Sep 9;159:111673. Epub 2022 Jul 9.

Sichuan Teway Food Group Co., Ltd, Chengdu, China. Electronic address:

Pre-salting is an important pre-treatment during production of Suancai as it provides flavor precursor and microbial community for subsequent fermentation. To investigate the effect of pre-salting duration on fermentation of Suancai, the physicochemical properties, microbial composition, non-volatile and volatile organic compounds profiles of Suancai pre-salted for 1 month (1 M) and 7 months (7 M) were analyzed during fermentation for 30 days. Results showed that 7 M led to higher salt content, faster depletion of reducing sugars, and more titratable acidity. Additionally, more lactic acid and acetic acid, and less umami amino acid (Glu) and GABA were observed in 7 M. Longer pre-salting duration (7 M) promoted formation of mild-flavor volatile compounds, and significantly reduced isothiocyanates with pungent off-flavor. Moreover, 7 M promoted abundance of genera Chromohalobacter, Vibrio and Pichia, while reducing abundance of Lactobacillus, Debaryomyces and Kazachstania throughout fermentation. These results implicated that longer pre-salting duration facilitated more acidic, milder flavor and less pungent off-odor in Suancai. This study provided a perspective for pre-salting as a control point for improving quality of fermented vegetable.
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http://dx.doi.org/10.1016/j.foodres.2022.111673DOI Listing
September 2022

Diterpenoids from the whole plant of Euphorbia wallichii and their protective effects on HO-induced BV-2 microglial cells injury.

Bioorg Chem 2022 Jul 30;128:106067. Epub 2022 Jul 30.

Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Thirteen undescribed diterpenoids, including an ent-isopimarane (1), ten ent-atisanes (2-8 and 15-17), and two ingenanes (20 and 21) and ten known compounds, were separated from the whole plant of E. wallichii. The structures and absolute stereochemistry of these compounds were delineated by 1D and 2D NMR, mass spectrometry, pyridine-induced solvent shifts, and X-ray diffraction analyses. Euphwanoid A (1) is elucidated as an ent-16‑norisopimarane type diterpenoid featuring a C-8-O-C-15 lactone fragment. And euphwanoid B (2) represents a rare ent-atisane type tetranorditerpene possessing a tetrahydrofuran moiety. In addition, all these isolated compounds were assayed for their protective effects on HO-induced BV-2 microglial cells damage. And representative compound 1 could protect BV-2 cells against oxidative damage via the NRF2/HO-1 signaling pathway.
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http://dx.doi.org/10.1016/j.bioorg.2022.106067DOI Listing
July 2022

Dramatic changes in aerosol composition during the 2016-2020 heating seasons in Beijing-Tianjin-Hebei region and its surrounding areas: The role of primary pollutants and secondary aerosol formation.

Sci Total Environ 2022 Jul 25;849:157621. Epub 2022 Jul 25.

Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

With the implementation of a series of air pollution mitigation strategies during the past decade, great air quality improvements have been observed in the BTH region. Despite of significant decreases in gaseous pollutants, such as SO and NO, the enhancement of secondary aerosol formation was observed. NO has surpassed SO and OM to become the dominant PM component. We find that the reduction of POC mainly dominated the decreasing trend of OC. As for secondary inorganic components, the key processes or factors controlling the spatial-temporal variation characteristics were different. The areas with large SO concentrations corresponded well to those with high SO concentrations, while the synchronized NO better followed spatial patterns in O than NO. From 2016 to 2020, the response of SO to SO was close to a linear function, while the reaction of NO to the decrease of NO displayed nonlinear behavior. Such different relationships indicated that SO was predominantly controlled by SO, while NO was not only related to NO but also determined by the secondary conversion process. The ratios of SO, NO, NH, and OC to EC between 2016 and 2020 were generally higher than 1 in typical BTH cities, and the ratio of NO to EC was exceptionally high, with a range reaching up to 200 %. Besides, this ratio coincided well with the enhancement of O, indicating the potential role of O to secondary NO formation. The diurnal cycle of NO, O, and NO concentration change rate indicated that the relative increase of O during nighttime may offset the effectiveness of NO emission reduction. This study provided observational evidence of enhanced secondary NO formation with the rising trend of atmospheric oxidation and emphasized the importance of nighttime chemistry for NO formation in the BTH region.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157621DOI Listing
July 2022

Combined Transcriptomics and Metabolomics Analyses in Grass Carp Under Anesthetic Stress.

Front Cell Infect Microbiol 2022 11;12:931696. Epub 2022 Jul 11.

National Pathogen Collection Center for Aquatic Animals, Shanghai Engineering Research Center of Aquaculture, National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China.

, as a common freshwater bony fish, is more susceptible to various diseases than other carp species, so it has been proposed as a test organism for toxicological analysis In this study, were anesthetized with MS-222 and 2-PE, and the related anesthetic mechanism and toxic effects were revealed by transcriptomics and metabolomics analyses. When the concentration of MS-222 was 80 mg/L and 200 mg/L, 179 and 887 differentially expressed genes (DEGs), respectively, were identified in the brain tissue of . When the concentration of 2-PE was 0.6 mL/L and 1.2 mL/L, 498 and 514 DEGs were identified. The DEGs associated with MS-222 treatment were enriched in immune pathways, lipid metabolism, amino acid metabolism, and various signaling pathways; DEGs associated with 2-PE treatment were enriched in immunity and amino acid metabolism. In total, 304 metabolites were identified using a combination of positive and negative ion modes in mass spectrometry. The common differential metabolites identified in the MS-222 high and low concentration groups were 20-HETE and 12(R)-HETE; the common significant differential metabolite identified in the 2-PE high and low concentration groups was salidroside. In combination with the transcriptomics analysis and metabolomics analysis, the results showed that with the MS-222 and 2-PE concentrations used in this experiment, the metabolism of arachidonic acid in was inhibited by MS-222, and 2-PE affected the upstream and downstream metabolic pathways of arachidonic acid metabolism, thereby affecting the metabolism of arachidonic acid. Both anesthetics induce sedation by affecting related metabolites that affect stress response and autoimmunity. Metabolomics results showed that neither anesthetic had a significant effect on cortisol expression.
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http://dx.doi.org/10.3389/fcimb.2022.931696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309352PMC
July 2022

Serum Oxylipin Profiles Identify Potential Biomarkers in Patients with Acute Aortic Dissection.

Metabolites 2022 Jun 23;12(7). Epub 2022 Jun 23.

Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.

Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (RX = 0.362 and RY = 0.807, = 0.03) and predictability (Q = 0.517, = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256-7.245, = 0.035; OR = 0.015, 95%CI:0.0002-0.3240, = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.
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http://dx.doi.org/10.3390/metabo12070587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324768PMC
June 2022

Effect of Financial Incentives on Hypertension Control: A Multicenter Randomized Controlled Trial in China.

Hypertension 2022 Jul 18:101161HYPERTENSIONAHA12219568. Epub 2022 Jul 18.

Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang (L.Z., S.L., Y.J., Y. Wang, Z.Y., Z.S.).

Background: Poorly controlled hypertension is a great challenge to global public health. Incentive approaches, based on behavioral and economic concepts, may improve patients' adherence to treatment.

Methods: We conducted a 2-arm randomized controlled trial to test whether financial incentives can help patients with poorly controlled hypertension in China reduce their blood pressure (BP). Participants were randomized 1:1 to the control and intervention groups. All participants received WeChat-based standard education and support for hypertension management. The intervention group received financial incentives, including process- and outcome-based incentives.

Results: No statistically significant differences in BP reduction and hypertension control rates were found between the two groups from baseline to 12-month follow-up. Mean systolic BP decreased from 158.7 to 149.8 mm Hg in the intervention group and 159.7 to 149.5 mm Hg in the control group (=0.639). Mean diastolic BP decreased from 93.7 to 86.6 mm Hg in the intervention group and 93.9 to 86.3 mm Hg in the control group (=0.667). Hypertension control rates in the intervention and control groups were 20.8% and 15.8%, respectively (=0.318). Medication adherence was 84.2% in the intervention group and 86.2% in the control group (=0.705).

Conclusions: Financial incentives were effective in the short term for BP control, but a sustained effect of incentive-based BP control was not identified beyond 3 months of intervention. Future studies that focus on identifying the appropriate amount and structure of financial incentives for BP control are warranted.

Registration: URL: xxx; Unique identifier: ISRCTN13467677.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.122.19568DOI Listing
July 2022

UV-fluorescence imaging for real-time non-destructive monitoring of pork freshness.

Food Chem 2022 Jul 12;396:133673. Epub 2022 Jul 12.

College of Engineering, China Agricultural University, Beijing 100083, China.

This study aimed to develop a cost-effective fluorescence imaging system to rapidly monitor pork freshness indicators during chilled storage. The system acquired fluorescence images of pork and the color features were extracted from these images to establish partial least squares regression (PLSR) models to predict total volatile basic nitrogen (TVB-N), total viable count (TVC), pH for pork. For TVB-N, TVC and pH values, R were 0.92, 0.88 and 0.74, residual predictive deviation (RPD) were 2.24, 2.03, and 1.19, respectively. For TVB-N and TVC indicators showed that the predictive ability of this model was largely comparable to that of fluorescence hyperspectral imaging. However, combining fluorescence and color imaging improved the model's predictive ability. For TVB-N, TVC and pH, R were 0.94, 0.93 and 0.85, RPD were 2.62, 2.59, and 1.95, respectively. Therefore, this study developed a system with great potential for detecting the value of most pork quality indicators in real-time.
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http://dx.doi.org/10.1016/j.foodchem.2022.133673DOI Listing
July 2022

Approved HIV reverse transcriptase inhibitors in the past decade.

Acta Pharm Sin B 2022 Apr 16;12(4):1567-1590. Epub 2021 Nov 16.

Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven B-3000, Belgium.

HIV reverse transcriptase (RT) inhibitors are the important components of highly active antiretroviral therapies (HAARTs) for anti-HIV treatment and pre-exposure prophylaxis in clinical practice. Many RT inhibitors and their combination regimens have been approved in the past ten years, but a review on their drug discovery, pharmacology, and clinical efficacy is lacking. Here, we provide a comprehensive review of RT inhibitors (tenofovir alafenamide, rilpivirine, doravirine, dapivirine, azvudine and elsulfavirine) approved in the past decade, regarding their drug discovery, pharmacology, and clinical efficacy in randomized controlled trials. Novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150 will be also highlighted. Future development may focus on the new generation of novel antiretroviral inhibitors with higher bioavailability, longer elimination half-life, more favorable side-effect profiles, fewer drug-drug interactions, and higher activities against circulating drug-resistant strains.
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http://dx.doi.org/10.1016/j.apsb.2021.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279714PMC
April 2022

Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-κB signaling in rabbit intrauterine adhesions endometrium.

Stem Cell Res Ther 2022 07 15;13(1):301. Epub 2022 Jul 15.

Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Purpose: The fundamental cause of intrauterine adhesions (IUAs) is the destruction and reduction in stem cells in endometrial basal layer, resulting in endometrial reconstruction very difficult. The purpose of this study was to investigate the effects and underlying mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on the endometrial reconstruction after transplantation.

Methods: hUCB-MSCs were isolated and identified by flow cytometry, osteogenic, adipogenic and chondrogenic differentiation assays. The rabbit IUA models were established and set five groups (control, 14/28th day after surgery, estrogen and hUCB-MSCs treatment). The number of endometrial glands and the fibrosis rate were evaluated using HE and Masson staining, respectively. Endometrial proliferation, angiogenesis and inflammation were evaluated by immunohistochemical staining of ER, Ki-67and TGF-β1, respectively. Single-cell RNA sequencing (scRNA-seq) was applied to explore the cell differentiation trajectory after hUCB-MSCs transplanted into IUA endometrium. Finally, molecular mechanism of hUCB-MSCs repairing damaged endometrium was investigated by RNA sequencing, qRT-PCR and Western blot assays.

Results: After transplantation of the hUCB-MSCs, the increase in endometrial gland number, estrogen receptor (ER) and Ki-67 expression, and the decrease in fibrosis rate and TGF-β expression (P < 0.05), suggested the endometrial repair, angiogenesis and inflammatory suppression. The therapeutic effect of hUCB-MSCs was significantly improved compared with 28th day after surgery and estrogen group. ScRNA-seq demonstrated that the transplanted hUCB-MSCs can trans-differentiate into endometrial cells: epithelial, fibroblast and macrophage. RNA sequencing of six IUA samples combined with qRT-PCR and Western blot assays further revealed that hUCB-MSCs may regulate Th17/Treg balance through NF-κB signaling, thus inhibiting the immune response of damaged endometrium.

Conclusions: Our study demonstrated that hUCB-MSCs can repair damaged endometrium through trans-differentiation, immunomodulatory capacities and NF-κB signaling, suggesting the treatment value of hUCB-MSCs in IUA.
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http://dx.doi.org/10.1186/s13287-022-02990-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284747PMC
July 2022

Action Recognition With Motion Diversification and Dynamic Selection.

IEEE Trans Image Process 2022 22;31:4884-4896. Epub 2022 Jul 22.

Motion modeling is crucial in modern action recognition methods. As motion dynamics like moving tempos and action amplitude may vary a lot in different video clips, it poses great challenge on adaptively covering proper motion information. To address this issue, we introduce a Motion Diversification and Selection (MoDS) module to generate diversified spatio-temporal motion features and then select the suitable motion representation dynamically for categorizing the input video. To be specific, we first propose a spatio-temporal motion generation (StMG) module to construct a bank of diversified motion features with varying spatial neighborhood and time range. Then, a dynamic motion selection (DMS) module is leveraged to choose the most discriminative motion feature both spatially and temporally from the feature bank. As a result, our proposed method can make full use of the diversified spatio-temporal motion information, while maintaining computational efficiency at the inference stage. Extensive experiments on five widely-used benchmarks, demonstrate the effectiveness of the method and we achieve state-of-the-art performance on Something-Something V1 & V2 that are of large motion variation.
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http://dx.doi.org/10.1109/TIP.2022.3189811DOI Listing
July 2022

A rare case report of renal ewing sarcoma/primitive neuroectodermal tumor with ACTH production.

BMC Urol 2022 Jul 11;22(1):103. Epub 2022 Jul 11.

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, China.

Background: Ewing sarcoma/primitive neuroectodermal tumor (PNET) of the renal is extremely rare. The common cause of ectopic ACTH syndrome is pulmonary neuroendocrine tumors, such as small cell carcinomas and carcinoid tumors. Here, we present an unusual case of ectopic ACTH syndrome and hypothyroidism caused by Ewing sarcoma/PNET of the right kidney.

Case Presentation: A 19-year-old girl presented with a history of right lumbar pain and discomfort for 2 months, aggravated for 2 days. Abdominal contrast-enhanced computed tomography and computed tomography angiography showed an upper pole occupancy of the right kidney occupancy with subepithelial hemorrhage. Preoperative hormone levels including plasma total cortisol (PTC), adrenocorticotrophic hormone (ACTH) and thyroid hormone measurements were abnormal, indicating that the patient had Cushing syndrome and hypothyroidism. The patient underwent right radical nephrectomy. Histopathological analysis revealed a renal small round blue cell tumor (consistent with a primitive neuroectodermal tumor), with positive immunohistochemistry for CD99 and Ki67 (about 10%) and molecular pathology for EWSR1 gene fusions. PTC, ACTH and thyroid hormone returned to normal after surgery.

Conclusions: We report a rare ectopic ACTH syndrome and hypothyroidism due to renal Ewing sarcoma/PNET. The clinical manifestation of renal Ewing sarcoma/PNET is non-specific and the diagnosis relies on pathological morphology, immunohistochemistry and fusion gene detection. At present, surgery combined with radiotherapy and chemotherapy is used in the treatment, but the prognosis is still not optimistic.
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http://dx.doi.org/10.1186/s12894-022-01055-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277804PMC
July 2022

A Review on the Prediction of Health State and Serving Life of Lithium-Ion Batteries.

Chem Rec 2022 Jul 4:e202200131. Epub 2022 Jul 4.

Institute of Advanced Materials, Nanjing Tech University, Nanjing, 210009, China.

The monitoring and prediction of the health status and the end of life of batteries during the actual operation plays a key role in the battery safety management. However, although many related studies have achieved exciting results, there are few systematic and comprehensive reviews on these prediction methods. In this paper, the current prediction models of remaining useful life of lithium-ion batteries are divided into mechanism-based models, semi-empirical models and data-driven models. Their advantages, technical obstacles, improvement methods and prediction performance are summarized, and the latest research results are shown by comparison. We highlight that the fusion models of convolution neural network, long short term memory network and so on, which have great practical application prospects because of their outstanding computing efficiency and strong modeling ability. Finally, we look forward to the future work in simplifying the model and improving its interpretability.
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http://dx.doi.org/10.1002/tcr.202200131DOI Listing
July 2022

Annexin-1 is an oncogene in glioblastoma and causes tumour immune escape through the indirect upregulation of interleukin-8.

J Cell Mol Med 2022 Aug 29;26(15):4343-4356. Epub 2022 Jun 29.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Annexin-1 (ANXA1) is widely reported to be deregulated in various cancers and is involved in tumorigenesis. However, its effects on glioblastoma (GBM) remain unclear. Using immunohistochemistry with tissue microarrays, we showed that ANXA1 was overexpressed in GBM, positively correlated with higher World Health Organization (WHO) grades of glioma, and negatively associated with poor survival. To further explore its role and the underlying molecular mechanism in GBM, we constructed ANXA1shRNA U87 and U251 cell lines for further experiments. ANXA1 downregulation suppressed GBM cell proliferation, migration, and invasion and enhanced their radiosensitivity. Furthermore, we determined that ANXA1 was involved in dendritic cell (DC) maturation in patients with GBM and that DC infiltration was inversely proportional to GBM prognosis. Considering that previous reports have shown that Interleukin-8 (IL-8) is associated with DC migration and maturation and is correlated with NF-κB transcriptional regulation, we examined IL-8 and p65 subunit expressions and p65 phosphorylation levels in GBM cells under an ANXA1 knockdown. These results suggest that ANXA1 significantly promotes IL-8 production and p65 phosphorylation levels. We inferred that ANXA1 is a potential biomarker and a candidate therapeutic target for GBM treatment and may mediate tumour immune escape through NF-kB (p65) activation and IL-8 upregulation.
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http://dx.doi.org/10.1111/jcmm.17458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344830PMC
August 2022

Biofilms on stone monuments: biodeterioration or bioprotection?

Trends Microbiol 2022 Sep 22;30(9):816-819. Epub 2022 Jun 22.

Environmental Science and Engineering Research Group, Guangdong Technion-Israel Institute of Technology (GTIIT), 241 Daxue Road, Shantou, Guangdong 515063, China; Guangdong Provincial Key Laboratory of Materials and Technologies for Energy Conversion, Guangdong Technion - Israel Institute of Technology, 241 Daxue Road, Shantou, Guangdong 515063, China. Electronic address:

Debate on whether biofilms on stone monuments are biodeteriorative or bioprotective is long-standing. We propose a criterion of 'relative bioprotective ratio' for assessing the ambivalent role of the biofilms by comparing biodeterioration with weathering. A boundary between biodeterioration and bioprotection exists and fluctuates with dynamic microflora influenced by environmental conditions.
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http://dx.doi.org/10.1016/j.tim.2022.05.012DOI Listing
September 2022

The kinetics of IgG subclasses and contributions to neutralizing activity against SARS-CoV-2 wild-type strain and variants in healthy adults immunized with inactivated vaccine.

Immunology 2022 Jun 25. Epub 2022 Jun 25.

Beijing Center for Disease Prevention and Control, Beijing, China.

Neutralizing antibody is an important indicator of vaccine efficacy, of which IgG is the main component. IgG can be divided into four subclasses. Up to now, studies analysing the humoral response to SARS-CoV-2 vaccination have mostly focused on measuring total IgG, and the contribution of specific IgG subclasses remains elusive. The aim of this study is to investigate the kinetics of neutralizing antibodies and IgG subclasses, and to explore their relationships in people vaccinated with inactivated COVID-19 vaccine. We conducted a prospective cohort study in 174 healthy adults aged 18-59 years old who were administrated 2 doses of CoronaVac 14 days apart and a booster dose 1 year after the primary immunization, and followed up for 15 months. Blood samples were collected at various time points after primary and booster immunization. We used live SARS-CoV-2 virus neutralizing assay to determine neutralizing ability against the wild-type strain and 4 variants (Beta, Gamma, Delta and Omicron) and ELISA to quantify SARS-CoV-2 RBD-specific IgG subclasses. The results showed that the 2-dose primary immunization only achieved low neutralizing ability, while a booster shot can significantly enhance neutralizing ability against the wild-type strain, Beta, Gamma, Delta and Omicron variants. IgG1 and IgG3 were the most abundant serum antibodies, and IgG2 and IgG4 were hardly detected at any time. The ratio of IgG1/IgG3 was positively associated with the neutralization ability. The underlying mechanism requires further exploration.
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http://dx.doi.org/10.1111/imm.13531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349727PMC
June 2022

Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.

Molecules 2022 Jun 9;27(12). Epub 2022 Jun 9.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.

A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation.
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http://dx.doi.org/10.3390/molecules27123721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230548PMC
June 2022

Revisiting the Transposon Evolution Revealing Extensive Involvement in the Shaping of Mammal Genomes.

Biology (Basel) 2022 Jun 16;11(6). Epub 2022 Jun 16.

College of Animal Science & Technology, Yangzhou University, Yangzhou 225009, China.

The data of this study revealed that was found in a wide variety of animal genomes, including 180 species from 36 orders of invertebrates and 145 species from 29 orders of vertebrates. An extensive invasion of was observed in mammals, with a high copy number. Almost 61% of those species contain more than 50 copies of ; however, 46% harbor intact elements, although the number of these intact elements is very low. Common HT events of elements were discovered across different lineages of animals, including mammals, that may have led to their widespread distribution, whereas and arthropods may have aided HT incidences. The activity of seems to be low in the kingdom of animals, most copies were truncated in the mammal genomes and lost their transposition activity, and transposons only display signs of recent and current activities in a few species of animals. The findings suggest that the family is important in structuring mammal genomes.
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http://dx.doi.org/10.3390/biology11060921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219625PMC
June 2022

G-protein couples MAPK cascade through maize heterotrimeric Gβ subunit.

Plant Cell Rep 2022 Aug 23;41(8):1763-1774. Epub 2022 Jun 23.

Jiangsu Key Laboratory of Crop Genetics and Physiology/Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, College of Agriculture, Yangzhou University, Yangzhou, 225009, China.

Key Message: G protein couples MAPK cascade through maize heterotrimeric Gβ subunit MGB1. Heterotrimeric G protein Gβ interacts with Gγ subunit to generate Gβγ dimer in modulation of various biological processes. The modulatory events at transcriptome scale of plant Gβ subunit remain largely unknown. To reveal the regulatory basis of Gβ subunit at transcriptome level, we first identified a canonical maize Gβ subunit MGB1 that physically interacted with Type C Gγ protein MGG4. For transcriptome analysis, two independent CRISPR/Cas9-edited MGB1 lines were generated, which all exhibited growth arrest, suggestive of MGB1 essential for maize seedling establishment. Transcriptomic outcomes showed that MGB1 knockout resulted in elevated transcriptional abundance of plant immune response marker PR and immune receptor RPM1. Integrated GO, KEGG, and GSEA analyses pinpointed the enrichment of differentially expressed genes in defense response pathway. Functional association network construction revealed MAPK cascade components and PR protein as hub regulators of MGB1-mediated immune signaling. MGB1 and scaffold protein ZmRACK1 together with MAPK cascade components coordinately modulated maize immune responses. We built a modulatory hierarchy of Gβ subunit at transcriptome and interacting scales, which is informative for our understanding of the regulatory basis of G protein signaling.
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http://dx.doi.org/10.1007/s00299-022-02891-wDOI Listing
August 2022

FCGBP Is a Promising Prognostic Biomarker and Correlates with Immunotherapy Efficacy in Oral Squamous Cell Carcinoma.

J Immunol Res 2022 12;2022:8443392. Epub 2022 Jun 12.

Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University & Hunan key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Changsha, 410008 Hunan, China.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck. In OSCC patients, the prognosis was dramatically different. In this research, we aimed to study the expressions and prognostic values of IgG Fc binding protein (FCGBP) in OSCC patients. The expression of FCGBP was analyzed using TCGA datasets and GEO datasets. FCGBP was evaluated for its predictive significance in OSCC patients by the use of a Kaplan-Meier and Cox regression model. Enrichment analysis for the GO and KEGG databases were conducted. CIBERSORT used TCGA datasets to show immune cell infiltration. In addition, researchers looked into the relationships between FCGBP and immune cells. The levels of FCGBP in OSCC cells was examined through the use of RT-PCR. FCGBP overexpression was tested for its effects on OSCC cell proliferation and invasion using CCK-8 and Transwell assays. We observed that FCGBP expressions were distinctly downregulated in OSCC specimens compared with nontumor tissues in both TCGA and GEO datasets, which was further confirmed by RT-PCR. OSCC patients with advanced clinical stages and poor prognoses had lower levels of FCGBP expression. Many immune-related biological activities and signaling pathways were found to be considerably abundant in KEGG tests and GO analysis results. The correlation analysis indicated that FCGBP was associated with a number of immune cells in a positive way. We found that FCGBP expressions were strongly and distinctly linked to the expressions of known immunological checkpoints, and FCGBP expression had significant positive connections with tumor mutational burden. FCGBP upregulation distinctly slowed the growth and invasion of OSCC cells in functional experiments. FCGBP has the potential to be a therapeutic target for OSCC and a biomarker for OSCC patients' prognosis.
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http://dx.doi.org/10.1155/2022/8443392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207623PMC
June 2022

A Framework to Predict the Molecular Classification and Prognosis of Breast Cancer Patients and Characterize the Landscape of Immune Cell Infiltration.

Comput Math Methods Med 2022 7;2022:4635806. Epub 2022 Jun 7.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

It is known that all current cancer therapies can only benefit a limited proportion of patients; thus, molecular classification and prognosis evaluation are critical for correctly classifying breast cancer patients and selecting the best treatment strategy. These processes usually involve the disclosure of molecular information like mutation, expression, and immune microenvironment of a breast cancer patient, which are not been fully studied until now. Therefore, there is an urgent clinical need to identify potential markers to enhance molecular classification, precision prognosis, and therapy stratification for breast cancer patients. In this study, we explored the gene expression profiles of 1,721 breast cancer patients through CIBERSORT and ESTIMATE algorithms; then, we obtained a comprehensive intratumoral immune landscape. The immune cell infiltration (ICI) patterns of breast cancer were classified into 3 separate subtypes according to the infiltration levels of 22 immune cells. The differentially expressed genes between these subtypes were further identified, and ICI scores were calculated to assess the immune landscape of BRCA patients. Importantly, we demonstrated that ICI scores correlate with patients' survival, tumor mutation burden, neoantigens, and sensitivity to specific drugs. Based on these ICI scores, we were able to predict the prognosis of patients and their response to immunotherapy. Together, these findings provide a realistic scenario to stratify breast cancer patients for precision medicine.
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http://dx.doi.org/10.1155/2022/4635806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201713PMC
June 2022

X-Linked Inhibitor of Apoptosis Protein (XIAP)-Loaded Magnetic Mesoporous Silica Nanoparticles Incorporated with miR-233 to Improve Radio Sensitization of Cervical Cancer Cells and Promote Apoptosis.

J Biomed Nanotechnol 2022 Mar;18(3):747-753

Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China.

This study investigated the impact of magnetic mesoporous silica nanoparticles (MMSN)-encapsulated X-linked inhibitor of apoptosis protein (XIAP) and miR-233 on tumor microenvironment in cervical cancer, to provide targeted treatment and strategy, to improve radio sensitization of cancer cells. Cervical cancer cells were treated with normal saline (control group), XIAP-loaded metallic mesoporous silica nanoparticles (MMSNs), and miR-233-targeted material (XIAP group, XIAP+miR-233 group). Proliferation, apoptosis and colony forming ability of cancer cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and colony formation experiments. experiments were established to observe the impact of XIAP-loaded MMSNs and miR-233 on tumor growth. Administration of XIAP-loaded MMSNs suppressed tumor growth of cervical cancer, and presence of miR-233 targeted material further decreased tumor volume, increasing radio sensitization of cancer cells. experiments confirmed that, combined treatment of XIAP and miR-233 suppressed cancer cell proliferation and invasion when inducing apoptosis. XIAP MMSNs characterized by large unit surface area, high dispersion and adhesion, and prolonged circulation time, improving drug delivery and treatment selectivity of chemotherapeutic drugs. This study suggests that XIAP MMSNs with miR-233 material suppress cervical cancer cell progression and tumor growth when augmenting radiosensitization of cancer cells, providing evidence for targeted therapy for the disease.
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http://dx.doi.org/10.1166/jbn.2022.3281DOI Listing
March 2022

A Methyl-Modified Silica Layer Supported on Porous Ceramic Membranes for the Enhanced Separation of Methyl Tert-Butyl Ether from Aqueous Solution.

Membranes (Basel) 2022 Apr 22;12(5). Epub 2022 Apr 22.

Faculty of Materials and Manufacturing, Beijing University of Technology, 100 Pingleyuan, Chaoyang District, Beijing 100124, China.

As a kind of volatile organic compound (VOC), methyl tert-butyl ether (MTBE) is hazardous to human health and destructive to the environment if not handled properly. MTBE should be removed before the release of wastewater. The present work supported the methyl-modified silica layer (MSL) on porous α-AlO ceramic membranes with methyltrimethoxysilane (MTMS) as a precursor and pre-synthesized mesoporous silica microspheres as dopants by the sol-gel reaction and dip-coating method. MTMS is an environmentally friendly agent compared to fluorinated alkylsilane. The MSL-supported AlO ceramic membranes were used for MTBE/water separation by pervaporation. The NMR spectra revealed that MTMS evolves gradually from an oligomer to a highly cross-linked methyl-modified silica species. Methyl-modified silica species and pre-synthesized mesoporous silica microspheres combine into hydrophobic mesoporous MSL. MSL makes the α-AlO ceramic membranes transfer from amphiphilic to hydrophobic and oleophilic. The MSL-supported α-AlO ceramic membranes (MSL-10) exhibit an MTBE/water separation factor of 27.1 and a total flux of 0.448 kg m h, which are considerably higher than those of previously reported membranes that are modified by other alkylsilanes via the post-grafting method. The mesopores within the MSL provide a pathway for the transport of MTBE molecules across the membranes. The presence of methyl groups on the external and inner surface is responsible for the favorable separation performance and the outstanding long-term stability of the MSL-supported porous α-AlO ceramic membranes.
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http://dx.doi.org/10.3390/membranes12050452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144733PMC
April 2022

Responses of human gut microbiota abundance and amino acid metabolism to berberine.

Food Funct 2022 Jun 6;13(11):6329-6337. Epub 2022 Jun 6.

Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

The intestine is a potential location for berberine (BBR) to exert its therapeutic effects, but the understanding of the influences of BBR on the gut microbiota is limited. Through fermentation of human intestinal microbiota, we investigated the effects of BBR on microbiota composition and metabolism. The result indicated that BBR reduced the production of acetic acid and propionic acid and had no effect on the content of butyric acid. Analysis of the 16S rRNA gene-based community revealed that BBR increased the abundance of and decreased the abundance of , and . Through metabolomics analysis, BBR treatment regulated various amino acid metabolism pathways of intestinal microbiota, especially tyrosine, serine and L-glutamate. Our study presented direct impacts of BBR on the intestinal microbiota, which provided the probable targets of the therapies by BBR and supported further exploration of the underlying mechanisms.
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http://dx.doi.org/10.1039/d1fo04003kDOI Listing
June 2022

[Clinical and genetic analysis of two rare male patients with Rett syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 May;39(5):488-493

Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450018, China.

Objective: To conduct clinical and genetic analysis of two male patients with atypical Rett syndrome.

Methods: Collection of clinical data in the two patients and these parents; whole exome sequencing (WES) was used to detect the potential variants, which were verified by Sanger sequencing. X chromosome inactivation (XCI) detection is performed in the Patient 1's mother to detect the allelic expression difference of the MECP2 gene.

Results: Patient 1, a 5-year and 10-month-old boy, had mental disorders and mild intellectual disability (ID) (IQ: 54), whose mother had ID. Patient 2 was a 9-month and 18-day-old male presented with recurrent infections, respiratory insufficiency, hypotonia and global developmental delay. WES indentified a hemizygous mutation, c.499C>T (p.R167W), in the MECP2 gene in patient 1, which was inherited from his mother. The inactivation of X chromosome is skewed, and the expression ratio of wild-type and mutant MECP2 is 100%:0. Patient 2 was found a de novo splicing mutation, c.62+2_62+3del in the MECP2 gene. They were both reported pathogenic variant related to Rett syndrome. c.499C>T (p.R167W) was defined as likely pathogenic (PS1+PM2+PP3) and c.62+2_62+3del was pathogenic (PVS1+PM2+PM6) based on American College of Medical Genetics and Genomics standards and guidelines.

Conclusion: Both the two patients were diagnosed with rare male Rett syndrome, which had atypical clinical manifestations and large difference. Above foundings have revealed novel phenotypes in Chinese male patients with Rett syndrome.
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http://dx.doi.org/10.3760.cma.j.cn511374-20210621-00517DOI Listing
May 2022

Effects of Prophylactic Administration of Granulocyte Colony-Stimulating Factor on Peripheral Leukocyte and Neutrophil Counts Levels After Chemotherapy in Patients With Early-Stage Breast Cancer: A Retrospective Cohort Study.

Front Oncol 2022 25;12:777602. Epub 2022 Apr 25.

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

Background: Both chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) frequently occur and can lead to dose-limiting toxicity and even fatal chemotherapy side effects. The prophylactic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF), including pegylated rhG-CSF (PEG-rhG-CSF), significantly reduces the risks of CIN and FN during chemotherapy in early-stage breast cancer (ESBC) patients. However, whether the prophylactic use of granulocyte colony-stimulating factor (G-CSF), especially PEG-rhG-CSF, can influence white blood cell (WBC) counts and absolute neutrophil counts (ANCs) after finishing the chemotherapy remains unknown. Therefore, exploring the development and recovery tendency of WBC counts and ANCs during and after chemotherapy is crucial.

Objective: We aimed to investigate the variation tendency and recovery of WBC counts and ANCs during and after chemotherapy and evaluate the independent factors influencing leukopenia and neutropenia lasting longer after chemotherapy. We also aimed to provide individualized prophylactically leukocyte elevation therapy for breast cancer patients.

Methods: This single-center retrospective cohort study evaluated 515 ESBC patients who received rhG-CSF or PEG-G-CSF for prophylaxis after adjuvant or neoadjuvant chemotherapy. Blood test reports were analyzed during chemotherapy, and on a 12-month follow-up period after finishing the chemotherapy. The WBC counts and ANCs were measured to assess their variation tendency characteristics and to identify independent factors that influenced the occurrence of leukopenia and neutropenia lasting longer than 12 months after chemotherapy.

Results: Prophylaxis with rhG-CSF or PEG-rhG-CSF kept the mean values of WBC counts and ANCs within the normal range during chemotherapy, but a significant difference in WBC levels was detected before the end of the last chemotherapy compared to the prechemotherapy period (baseline) ( < 0.001). During the 12-month follow-up after the end of the last chemotherapy, WBC counts and ANCs gradually recovered, but the group that used only PEG-rhG-CSF (long-acting group, = 0.012) or rhG-CSF (short-acting group, = 0.0005) had better leukocyte elevation effects than the mixed treatment group (PEG-rhG-CSF mixed rhG-CSF). Besides, the short-acting group had a better neutrophil elevation effect than the longer-acting ( = 0.019) and mixed ( = 0.002) groups. Leukopenia was still present in 92 (17.9%) patients and neutropenia in 63 (12.2%) 12 months after the end of the last chemotherapy. The duration of leukopenia over 12 months was closely associated with the baseline WBC level ( < 0.001), G-CSF types ( = 0.027), and surgical method ( = 0.041). Moreover, the duration of neutropenia over 12 months was closely related to the baseline ANC ( < 0.001), G-CSF types ( = 0.043), and molecular typing ( = 0.025).

Conclusion: The prophylactic application of G-CSF effectively stabilized the WBC counts and ANCs during chemotherapy in ESBC patients. Nevertheless, the recovery of WBC counts and ANCs after chemotherapy varied between different G-CSF treatment groups. The risk of leukopenia and neutropenia persisting for more than 12 months after chemotherapy was associated with G-CSF types, the baseline level of WBC count/ANCs, surgical method, and molecular typing.
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http://dx.doi.org/10.3389/fonc.2022.777602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084938PMC
April 2022

First Report of Powdery Mildew Caused by Erysiphe polygoni on Trifolium repens in China.

Plant Dis 2022 May 10. Epub 2022 May 10.

Lanzhou Jiaotong University, 88 West Road, Anning District, lanzhou, China, 730070;

White clover (Trifolium repens L.) belongs to the Fabaceae family legume and is cultivated in China for its medicinal properties and ornamental value. White clover is grown around the world for forage, turf , green manure and soil conservation purposes (Zhang el al. 2016). In October 2021, an investigation of a 1,000 m2 plant nursery in Lanzhou, China (36°06'N, 103°83'E) found that 80% of White clover plants were infected, and powdery mildew covered 95% of the leaf area. The disease had seriously destroyed the forage quality and reduced the ornamental value. Initially, thin, radial, irregular white colonies appeared on leaves and gradually spread to stems. The white colonies then expanded and thickened to cover upper surface of the leaf, and microscopic hyphae appeared on the bottom of the leaf. In severe cases, the infection resulted in dieback of the leaf. A small area of sporulating fungus was stripped off from the leaf surface with tape and mounted in sterile water for microscopic examination (Mukhtar et al. 2017). Conidiophores were cylindrical, consisting of a foot cell followed by three to four short cells, measuring 75 to 160 × 7 to 10 μm. Conidiophores had straight, cylindric foot cells ranging from 25 to 40 µm long. Singly produced conidia were hyaline and ranged in shape from oblong to cylindrical. Conidia lacked distinct fibrotic bodies and measured 30 to 45 × 15 to 25 μm in length. Long, unbranched germ tubes formed from the ends of the conidia and nipple-shaped appressoria developed on epiphytic mycelia. Based on these morphological characteristics, the pathogen was initially identified morphologically as Erysiphe polygoni (Braun and Cook 2012). To validate the identity, the internal transcribed spacer (ITS) region of the pathogen (SY77) rDNA was amplified by PCR and sequenced using the ITS1/ITS4 primers (White et al. 1990). The resulting sequences were registered to GenBank (GenBank Accession No.OM280998). The ITS sequence of the SY77 was 100% (640/640) identical to E. polygoni (LC009892) on Polygonum aviculare in the United Kingdom and 99% (638/640) identical to E. polygoni (MK685172) on Antigonon leptopus in Taiwan. MEGA 7.0 was used to conduct the neighbor-joining phylogenetic analysis using the ITS sequences from GenBank. The data indicated that the strain SY77 and E. polygoni clustered together on the same branch. Pathogenicity tests were conducted by gently pressing the infected leaves onto five healthy potted White clover plants, while five non-inoculated plants were used as controls (Michael et al. 2021). The plants were maintained in a growth chamber (25 ℃, 14 h light, and 10 h dark period, RH > 80%). After 10 days, the inoculated plants developed powdery mildew symptoms, whereas the control plants remained symptom-free. The fungus on the inoculated plants was re-isolated, re-identified, and confirmed as E. polygoni based on morphological observations and molecular identification. There is no previous report on E. polygoni causing powdery mildew on White clover in China. The powdery mildew caused by E. polygoni on Red clover has been reported in China and Bulgaria, respectively (Yuan el al.1991; Galina el al. 2017). To our knowledge, this is the first report of powdery mildew caused by E. polygoni on White clover in China. References: 1. Zheng, L., et al. 2018. Plant Dis. 102:628. 2. Mukhtar, G., et al. 2017. Plant Dis.101:1, 246. 3. Braun, U., and Cook, R. T. A. 2012. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht. 4. Michael, R. F., et al. 2021.Plant Dis. First look.( doi.org/ 10.1094/PDIS-09-21-2060-PDN). 5. Yuan, Q. H., el al.1991. Pratacult Sci.05:59 (in Chinese). 6. Galina, N., et al, 2017. BIOTECHNOL Anim Husb.33.127.
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http://dx.doi.org/10.1094/PDIS-02-22-0289-PDNDOI Listing
May 2022

Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis.

Drug Des Devel Ther 2022 3;16:1301-1309. Epub 2022 May 3.

Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, USA.

Introduction: The phosphodiesterase 4 (PDE4) inhibitor, rolipram, has beneficial effects on tissue inflammation, injury and fibrosis, including in the liver. Since rolipram elicits significant CNS side-effects in humans (ie, nausea and emesis), our group developed a fusogenic lipid vesicle (FLV) drug delivery system that targets the liver to avoid adverse events. We evaluated whether this novel liposomal rolipram formulation reduces emesis.

Methods: C57Bl/6J male mice were used to compare the effect of three doses of free and FLV-delivered (FLVs-Rol) rolipram in a behavioral correlate model of rolipram-induced emesis. Tissue rolipram and rolipram metabolite levels were measured using LC-MS/MS. The effect of FLVs-Rol on brain and liver PDE4 activities was evaluated.

Results: Low and moderate doses of free rolipram significantly reduced anesthesia duration, while the same doses of FLVs-Rol had no effect. However, the onset and duration of adverse effects (shortening of anesthesia period) elicited by a high dose of rolipram was not ameliorated by FLVs-Rol. Post-mortem analysis of brain and liver tissues demonstrated that FLVs affected the rate of rolipram uptake by liver and brain. Lastly, administration of a moderate dose of FLVs-Rol attenuated endotoxin induced PDE4 activity in the liver with negligible effect on the brain.

Discussion: The findings that the low and moderate doses of FLVs-Rol did not shorten the anesthesia duration time suggest that FLV delivery prevented critical levels of drug from crossing the blood-brain barrier (BBB) to elicit CNS side-effects. However, the inability of high dose FLVs-Rol to prevent CNS side-effects indicates that there was sufficient unencapsulated rolipram to cross the BBB and shorten anesthesia duration. Notably, a moderate dose of FLVs-Rol was able to decrease PDE4 activity in the liver without affecting the brain. Taken together, FLVs-Rol has a strong potential for clinical application for the treatment of liver disease without side effects.
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http://dx.doi.org/10.2147/DDDT.S355796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078351PMC
May 2022

A label-free and ultrasensitive electrochemical biosensor for oral cancer overexpressed 1 gene exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies.

Analyst 2022 May 30;147(11):2412-2424. Epub 2022 May 30.

Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, College of Chemistry and Materials, Nanning Normal University, Nanning 530001, P. R. China.

A label-free and ultrasensitive electrochemical biosensor for oral cancer overexpressed 1 (ORAOV1) gene was constructed exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies. Capture DNA with a sulfhydryl group at its 3' terminus was modified onto the surface of a bare gold electrode an Au-S bond. Assisted DNA hybridized with basal DNA to form hybrid DNA in advance, and ORAOV1 gene hybridized continuously with such a hybrid DNA from the other terminus to construct intact double-stranded DNA. Exonuclease III digested basal DNA in such intact double-stranded DNA specifically, and both ORAOV1 gene and assisted DNA were released into solution. ORAOV1 gene induced another intact double-stranded DNA digestion for target recycling, while assisted DNA hybridized with the capture DNA to form double-stranded DNA on the modified electrode surface. Unhybridized capture DNA on the modified electrode surface was hydrolyzed by RecJf exonuclease to reduce the background electrochemical signal. The 3' terminus of double-stranded DNA on the modified electrode surface was prolongated to be guanine-rich oligonucleotides under the catalysis of terminal deoxynucleotidyl transferase. In the presence of K ions, hemin adsorbed onto guanine-rich oligonucleotides to construct a G-quadruplex/hemin complex with a large steric hindrance effect to efficiently avoid the charge transfer of the [Fe(CN)] probe toward the electrode surface. The electrochemical impedance value was increased significantly after the addition of ORAOV1 gene exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies. The electrochemical impedance value was linearly related to the logarithmic concentration of ORAOV1 gene in the range from 0.05 fM to 20 pM, and the detection limit of ORAOV1 gene was low to 0.019 fM. This biosensor was used to detect ORAOV1 gene in complicated human saliva samples with satisfactory results.
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http://dx.doi.org/10.1039/d2an00367hDOI Listing
May 2022

Status of Humoral and Cellular Immune Responses within 12 Months following CoronaVac Vaccination against COVID-19.

mBio 2022 06 27;13(3):e0018122. Epub 2022 Apr 27.

Beijing Center for Disease Prevention and Control, Beijing Research Center for Preventive Medicine, Beijing, China.

Understanding immune memory to COVID-19 vaccines is critical for the design and optimal vaccination schedule for curbing the COVID-19 pandemic. Here, we assessed the status of humoral and cellular immune responses at 1, 3, 6, and 12 months after two-dose CoronaVac vaccination. A total of 150 participants were enrolled, and 136 of them completed the study through the 12-month endpoint. Our results show that, at 1 month after vaccination, both binding and neutralizing antibodies could be detected; the seropositive rate of binding antibodies and seroconversion rate of neutralizing antibodies were 99% and 50%, respectively. From 3 to 12 months, the binding and neutralizing antibodies declined over time. At 12 months, the binding and neutralizing antibodies were still detectable and significantly higher than the baseline. Gamma interferon (IFN-γ) and interleukin 2 (IL-2) secretion specifically induced by the receptor-binding domain (RBD) persisted at high levels until 6 months and could be observed at 12 months, while the levels of IL-5 and granzyme B (GzmB) were hardly detected, demonstrating a Th1-biased response. In addition, specific CD4 T central memory (T), CD4 effector memory (T), CD8 T, and CD8 terminal effector (T) cells were all detectable and functional up to 12 months after the second dose, as the cells produced IFN-γ, IL-2, and GzmB in response to stimulation of SARS-CoV-2 RBD. Our work provides evidence that CoronaVac induced not only detectable binding and neutralizing antibody responses, but also functional SARS-CoV-2-specific CD4 and CD8 memory T cells for up to 12 months. CoronaVac is an inactivated vaccine containing whole-virion SARS-CoV-2, which has been approved in 43 countries for emergency use as of 26 November 2021. However, the long-term immune persistence of the CoronaVac vaccine is still unknown. Here, we reported the status of the persistence of antibodies and cellular responses within 12 months after two doses of CoronaVac. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.
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http://dx.doi.org/10.1128/mbio.00181-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239277PMC
June 2022
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