Publications by authors named "Mei Wang"

1,619 Publications

  • Page 1 of 1

Identification, tissue distribution, and anorexigenic effect of amylin in Siberian sturgeon (Acipenser baeri).

Comp Biochem Physiol A Mol Integr Physiol 2021 Sep 14:111079. Epub 2021 Sep 14.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China. Electronic address:

Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon.
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http://dx.doi.org/10.1016/j.cbpa.2021.111079DOI Listing
September 2021

The Role of IL-37 and IL-38 in Obstetrics Abnormalities.

Authors:
Mei Wang

Front Med (Lausanne) 2021 27;8:737084. Epub 2021 Aug 27.

Department of Obstetrics and Gynaecology, Gansu Provincial Hospital, Lanzhou, China.

There are two fairly common complications during pregnancy, i.e., gestational diabetes mellitus (GDM) and pre-eclampsia, which are independent, but are also closely linked in prevalence in pregnant women, with potential serious adverse consequences. IL-37 and IL-38, which belong to the IL-1 superfamily, participate in anti-inflammatory responses. Dysregulation of IL-37 and IL-38 has been observed in many auto-immune diseases. IL-37 is substantially reduced in the umbilical cords and placentas of GDM subjects, but IL-37 is significantly induced in the placentas of pre-eclampsia patients, suggesting there are differential regulatory roles of IL-37 in obstetrics, despite IL-37 being an anti-inflammatory mediator. Furthermore, IL-38 is substantially increased in the umbilical cords and placentas of GDM subjects, but minimal difference is observed in the placentas from pre-eclampsia patients. These data imply that IL-38 is also regulated independently within the diseased placentas. This review provides some insight for both basic scientists and medical practitioners to manage these patients effectively.
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http://dx.doi.org/10.3389/fmed.2021.737084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429600PMC
August 2021

Key indicators for renewal and reconstruction of perennial trees soil: Microorganisms and phloridzin.

Ecotoxicol Environ Saf 2021 Sep 1;225:112723. Epub 2021 Sep 1.

State Key Laboratory of Crop Biology/College of Horticultural Science and Engineering, Shandong Agricultural University, Tai'an 271018, Shandong, China. Electronic address:

Perennial tree soil inhibits the growth of replanting apples, but the mechanism that underlies this inhibition is poorly understood. A total of 57 perennial tree soils were selected for the collection of soil samples in the Bohai Bay in May 2018. The severity of apple replant disease (ARD) for each soil was determined by calculating the rate of inhibition of growth replanted apple trees. A high-throughput sequencing analysis of internal transcribed spacer (ITS) was used to determine the soil fungal community. A correlation analysis was used to determine the relationship between the rate of inhibition of apple growth and soil factors. The degree of inhibition of plant growth varied substantially among the 57 soil samples examined. Different perennial tree soils have varying degrees of ARD. There was no significant difference in the composition of fungal community at the phylum level, but the genus level differed substantially. The abundances of Fusarium and Mortierella species and the contents of phloridin in the soil and soil organic matter (SOM) were significantly correlated with ARD severity. Structural equation modeling also emphasized that the degree of occurrence of ARD was directly or indirectly affected by Fusarium, Mortierella, phloridin and SOM. A correlation analysis can only be used as an indicator, and further research is merited to reveal how soil parameters affect ARD.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112723DOI Listing
September 2021

Simultaneous removal of Cr and organic matters via coupling Cr-Fenton-like reaction with Cr flocculation: The key role of Cr flocs on coupling effect.

Chemosphere 2021 Aug 26;287(Pt 1):131991. Epub 2021 Aug 26.

Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Qingdao, 266200, China. Electronic address:

Cr contamination is frequently combined with organic pollution. Cr flocculation using flocculants results in difficulty in Cr recovery and increase of salinity. Moreover, the fates of coexisted organic pollutants are rarely attended. In this study, the Fenton-like reaction based on Cr redox reaction (Cr-Fenton-like reaction) coupled with Cr flocculation was established using HO as additives, which gave the opportunity to realize simultaneous removal of Cr and organic matters sustainably. In the coupling system, Cr-Fenton-like reaction generated more OH for Cr flocculation via the HO decomposition, meanwhile, Cr flocculation provided heterogeneous catalytic regions for Cr-Fenton-like reaction. The formation of Cr flocs was the key to the coupling effect. They created partially alkaline regions, therefore Cr-Fenton-like reaction (reaction condition: pH > 5) and Cr flocculation (reaction condition: pH > 8) occurred in these heterogeneous regions, although the pH of the solutions was below 5. Besides, the Cr flocs in the coupling system tended to adsorb Cr(III) which also contributed to the coupling effect. Although Cr-Fenton-like reaction generated Cr(VI) inevitably, the dissolved Cr(VI) didn't accumulate due to the persistent acidic condition and the heterogeneous catalysis of Cr flocs in the coupling system. When the coupling effect was applied to a stimulated tannery wastewater with Cr and organic co-pollution, the simultaneous removal rates for Cr and total organic carbon were 81.2% and 41.34% respectively after an 8-h running. This study gives deep insights into the coupling effect and provides a sustainable and eco-friendly strategy for the remediation of wastewater with Cr and organic co-pollution.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131991DOI Listing
August 2021

An efficient manganese-oxidizing fungus Cladosporium halotolerans strain XM01: Mn(II) oxidization and Cd adsorption behavior.

Chemosphere 2021 Aug 26;287(Pt 1):132026. Epub 2021 Aug 26.

State Environmental Protection Key Laboratory of Synergetic Control and Joint Remediation for Soil and Water Pollution, College of Ecology and Environment, Chengdu University of Technology, Chengdu, 610059, Sichuan, China. Electronic address:

The applications of biogenic Mn oxides (BMOs) formed by Mn-oxidizing fungus in decontaminating heavy metals have attracted increasing attention. In this study, an efficient Mn-oxidizing fungus was isolated from soil and identified as Cladosporium halotolerans strain XM01. The Mn(II) adsorption and oxidation activities of this strain were investigated, showing significantly high removal and oxidation rates of soluble Mn(II) of 99.9% and 88.2%, respectively. Dynamic analysis of the Mn(II) removal process demonstrated the oxidation process of Mn(II) to Mn(III) was the rate-limiting step in the Mn(II) metabolic process. The XRD and SAED characterization showed that more layers were orderly accumulated along the c-axis with the formation of fungal BMOs, which might lead to the decrease in its specific surface area. The adsorption of Cd(II) by the formed BMOs was investigated and compared with two typical abiotic Mn oxides, indicating that the adsorption capacity decreased with the following order: immature BMO, mature BMO, δ-MnO, acid birnessite, while the fixation capacity decreased in the order of acid birnessite, mature BMO, δ-MnO, immature BMO. The inverse correlation between the capacity of Cd(II) adsorption and fixation of immature and mature BMOs was probably attributed to the increase in the layer stacking of BMOs. This result indicates an interesting phenomenon of high reservation of Cd(II) resulting from sequential transformation from strong adsorption to strong fixation with the formation of BMOs. This study offers considerable insights into fungal Mn oxidation mechanisms and provides theoretical guidance for fungal BMOs in heavy metals bioremediation.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132026DOI Listing
August 2021

Trust in Government Actions During the COVID-19 Crisis.

Soc Indic Res 2021 Aug 24:1-23. Epub 2021 Aug 24.

WHU - Otto Beisheim School of Management, Vallendar, Germany.

The worldwide COVID-19 pandemic puts countries and their governments in an unprecedented situation. Strong countermeasures have been implemented in most places, but how much do people trust their governments in handling this crisis? Using data from a worldwide survey, conducted between March 20th and April 22nd, 2020, with more than 100,000 participants, we study people's perceptions of government reactions in 57 countries. We find that media freedom reduces government trust directly as well as indirectly via a more negative assessment of government reactions as either insufficient or too strict. Higher level of education is associated with higher government trust and lower tendency to judge government reactions as too extreme. We also find different predictors of perceived insufficient reactions vs. too-extreme reactions. In particular, number of COVID-19 deaths significantly predicts perceived insufficient reactions but is not related to perceived too-extreme reactions. Further survey evidence suggests that conspiracy theory believers tend to perceive government countermeasures as too strict.
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http://dx.doi.org/10.1007/s11205-021-02772-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383026PMC
August 2021

[email protected] Nanowire Arrays on Flexible Graphite Paper with Tunable Persistent Photoconductivity.

ACS Appl Mater Interfaces 2021 Sep 27;13(35):41916-41925. Epub 2021 Aug 27.

Department of Physics, Department of Materials Science and Engineering, and Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon 518057, Hong Kong, China.

Flexible optoelectronic synaptic devices that functionally imitate the neural behavior with tunable optoelectronic characteristics are crucial to the development of advanced bioinspired neural networks. In this work, amorphous oxide-decorated GaN nanowire arrays ([email protected] NWAs) are prepared on flexible graphite paper. A [email protected] NWA-based flexible device has tunable persistent photoconductivity (PPC) and shows a conversible fast/slow decay process (SDP). Photoconductivity can be modulated by single or double light pulses with different illumination powers and biases. PPC gives rise to the high-performance SDP such as a long decay time of 2.3 × 10 s. The modulation mechanism is proposed and discussed. Our results reveal an innovative and efficient strategy to produce decorated NWAs on a flexible substrate with tunable optoelectronic properties and exhibit potential for flexible neuromorphic system applications.
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http://dx.doi.org/10.1021/acsami.1c13355DOI Listing
September 2021

Metastasis suppressor 1 interacts with α-actinin 4 to affect its localization and regulate formation of membrane ruffling.

Cytoskeleton (Hoboken) 2021 Aug 25. Epub 2021 Aug 25.

The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.

Membrane ruffling plays an important role in the directed cell migration and escape of tumor cells from the monolayer. Metastasis suppressor 1 (MTSS1), also known as missing in metastasis, has been implicated in cell morphology, motility, metastasis, and development. Here, the dynamic interaction proteins associated with MTSS1 and involved in membrane ruffling were determined by cross-linking and mass spectrometry analysis. We identified α-actinin 4 (ACTN4) as an interacting protein and confirmed a direct interaction between MTSS1 and ACTN4. Moreover, co-expression of MTSS1 in fibroblasts recruited cytoplasmic ACTN4 to the cell periphery, at which point ruffling became thick and rigid. In MCF-7 cells, MTSS1 knockdown did not show an obvious effect on the cell shape or the distribution of endogenous ACTN4; however, ACTN4 overexpression transformed cell morphology from an epidermal- to a fibroblast-like shape, and further MTSS1 depletion significantly increased the ratio of fibroblast cells exhibiting prominent ruffling. Furthermore, biochemical data suggested that MTSS1 cross-linking with ACTN4 induced the formation of actin fiber bundles into more organized structures in vitro. These data indicated that MTSS1 might recruit cytoplasmic ACTN4 to the cell periphery and regulate cytoskeleton dynamics to restrict its performance in membrane ruffling.
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http://dx.doi.org/10.1002/cm.21686DOI Listing
August 2021

The Cardiorespiratory fitness of children and adolescents in Tibet at altitudes over 3,500 meters.

PLoS One 2021 19;16(8):e0256258. Epub 2021 Aug 19.

National Physical Fitness Research Center, China Institute of Sport Science, Dongcheng, Beijing, China.

Background: Cardiorespiratory fitness (CRF) is the core element of health-related physical fitness evaluation. High pressure and low oxygen in Tibet (over 3,500 m above sea level) may negatively impact the residents' CRF. The 20-m shuttle run test (20mSRT) is the most popular field-based assessment and estimate of CRF in children and adolescents worldwide. However, normative CRF data for the children and adolescents residing in China's plateau region are unavailable, which prevents comparability among those living at high-altitudes around the world.

Purpose: To measure the CRF of Chinese children and adolescents aged 9-18 years living in Tibet at altitudes exceeding 3,500 m, and to identify correlations between this metric and demographic characteristics (age, sex, and ethnicity). These data were then compared with those generated in the lowland (Shanghai, China) and various global regions.

Methods: 20mSRT performance (number of completed laps) and predicted peak oxygen consumption (VO2peak) were used as indicators of CRF. We measured the CRF of 1,717 healthy children and adolescents aged 9-18 years living in Tibet. The CRF data from school-age subjects in Shanghai (2,437 boys and 2,396 girls) and worldwide (1,142,026 students from 50 countries/regions in Africa, Asia, Europe, Latin America, North America, and Oceania) were collated from published papers.

Results: The average CRF of the participants from Tibet was 39.8 mL/kg/min. The male subjects (n = 876; 41.1 ± 4.42 mL/kg/min) had a higher average CRF than their female counterparts (n = 841; 37.8 ± 5.40 mL/kg/min). CRF decreased with age in both sexes at statistical significance (F = 1249.9, p for trend 0.05). The indigenous Tibetans (n = 1289; 40.1 ± 3.71 mL/kg/min) had a significant higher average CRF than those of Han descent (n = 394; 38.9 ± 4.70 mL/kg/min) (p < 0.05).

Conclusions: Children and adolescents aged 7-18 years residing above 3,500 m in Tibet displayed lower CRF traits compared with their counterparts from the plains area and other high altitude places. CRF varied according to age, sex, and ethnic group. Given the importance of CRF in children and adolescents, effective intervention strategies should be implemented to improve CRF in children and adolescents on the plateau.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256258PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375997PMC
August 2021

Chemical Constituents and Anti-Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair.

Chem Biodivers 2021 Aug 17:e2100214. Epub 2021 Aug 17.

Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, 571199, P. R. China.

The essential oil (EO) of the herbal pair (HP), Alpinia officinarum-Cyperus rotundus (HP G-X) has been conventionally used in traditional Chinese medicine (TCM) for 'warming the stomach' and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti-gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G-X and its corresponding single herbs were analyzed using GC/MS. A total of 74, 56, and 85 compounds were detected in A. officinarum (GLJ), C. rotundus (XF), and HP G-X, accounting for 93.2 %, 89.5 %, and 92.0 % of the total content, respectively. GLJ mainly contains 1,8-cineol (22.0 %) and α-terpineol (11.8 %), whereas cyperenone (22.4 %) and cyperene (12.3 %) were the major constituents in XF. These four compounds were also detected in the HP G-X with relatively high composition as 11.8 %, 5.5 %, 11.8 %, and 10.6 %, respectively. Although no new compounds were detected in HP G-X, the relative concentration of some compounds increased, while others decreased or even disappeared. HP G-X showed the lowest toxicity (TC >800 μg/mL) against human gastric mucosal epithelial cells (GES-1) and had the best protective effect against ethanol-induced GES-1 cell damage compared to the individual herbs. In vitro studies demonstrated that HP G-X and the corresponding single herbs significantly reduced IL-6, TNF-α, and COX-2. In addition, in vivo investigations indicated that HP G-X can protect the gastric mucosa of mice from ethanol-induced damage by inhibiting the inflammatory reaction and providing analgesia. It can also inhibit the expression of NF-κBp65, COX-2, and TRPV1 protein, reduce the concentrations of IL-6 and TNF-α, and relieve heat-induced pain. This study further substantiated the traditional application of HP G-X against gastric ulcers through both in vivo and in vitro investigations.
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http://dx.doi.org/10.1002/cbdv.202100214DOI Listing
August 2021

Corrigendum to "Fabrication of BiFeO-g-CN-WO Z-scheme heterojunction as highly efficient visible-light photocatalyst for water reduction and 2,4-dichlorophenol degradation: Insight mechanism" [J. Hazard. Mater. 397 (2020) 122708].

J Hazard Mater 2021 Aug 7;421:126772. Epub 2021 Aug 7.

Engineering Research Center for Functional Ceramics of the Ministry of Education, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, PR China; China-EU Institute for Clean and Renewable Energy, Huazhong University of Science and Technology, Wuhan 430074, PR China.

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http://dx.doi.org/10.1016/j.jhazmat.2021.126772DOI Listing
August 2021

Equal-intensity beam splitter fabricated by segmented half-wave plate for passive laser speckle reduction.

Opt Lett 2021 Aug;46(16):3965-3968

An equal-intensity beam splitter (EIBS) for passive laser speckle reduction is reported. The EIBS consists of a segmented half-wave plate (SHWP) with the designed orientation of the fast axis of each segment, a polarization beam splitter, and a mirror. The SHWP is fabricated using patterned photoalignment material and liquid crystal polymer. Ten laser sub-beams are generated by the twenty-one-pixelated EIBS, where the largest intensity ratio among them is 7.6. Laser temporal and spatial coherences are destroyed because of the optical path delays among the laser sub-beams. The EIBS is used to reduce laser speckle passively, and objective speckle contrast is reduced from 0.82 to 0.33 when all 10 laser sub-beams are used.
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http://dx.doi.org/10.1364/OL.431405DOI Listing
August 2021

Meta Balanced Network for Fair Face Recognition.

IEEE Trans Pattern Anal Mach Intell 2021 Aug 12;PP. Epub 2021 Aug 12.

Although deep face recognition has achieved impressive progress in recent years, controversy has arisen regarding discrimination based on skin tone, questioning their deployment into real-world scenarios. In this paper, we aim to systematically and scientifically study this bias from both data and algorithm aspects. First, using the dermatologist approved Fitzpatrick Skin Type classification system and Individual Typology Angle, we contribute a benchmark called Identity Shades (IDS) database, which effectively quantifies the degree of the bias with respect to skin tone in existing face recognition algorithms and commercial APIs. Further, we provide two skin-tone aware training datasets, called BUPT-Globalface dataset and BUPT-Balancedface dataset, to remove bias in training data. Finally, to mitigate the algorithmic bias, we propose a novel meta-learning algorithm, called Meta Balanced Network (MBN), which learns adaptive margins in large margin loss such that the model optimized by this loss can perform fairly across people with different skin tones. To determine the margins, our method optimizes a meta skewness loss on a clean and unbiased meta set and utilizes backward-on-backward automatic differentiation to perform a second order gradient descent step on the current margins. Extensive experiments show that MBN successfully mitigates bias and learns more balanced Performance for people with different skin tones in face recognition.
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http://dx.doi.org/10.1109/TPAMI.2021.3103191DOI Listing
August 2021

Simultaneous Tuning Band Gaps of Cu2O and TiO2 to form S-Scheme Hetero-Photocatalyst.

Chemistry 2021 Aug 11. Epub 2021 Aug 11.

Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, the State Key laboratory for oxo synthesis and selective oxidation, Tianshui middle Road, 730000, Lanzhou, CHINA.

Photocatalytic Z or S scheme merits higher redox potentials and faster charge separation. However, heterostructure photocatalyst having band gaps of bulk materials often has a type I band structure leading to poor photocatalytic activity. In view of this, we report simultaneous tuning of band gaps of Cu 2 O and TiO 2 , where quantum dot Cu 2 O nanoparticles were formed on doped TiO 2 with Ti 3+ . The shrunk size of Cu 2 O made its conduction band more negative while the introduction of Ti 3+ made absorption edge red shift to visible light region. The as-formed heterostructure enabled S-Scheme mechanism with remarkable activity and stability for visible light photodegradation of 4-chlorophenol (4-CP). The as-obtained photocatalysts' activity demonstrated ca. 510 folds increase as compared to individual ones and mechanical blend. The as-obtained photocatalysts maintained over 80% for 5 cycles and 2 months exposure to O 2 did not decrease degradation rate. ESR characterization and scavengers' experiments proved S-Scheme mechanism.
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http://dx.doi.org/10.1002/chem.202102120DOI Listing
August 2021

Circulating LIPCAR is a potential biomarker of heart failure in patients post-acute myocardial infarction.

Exp Biol Med (Maywood) 2021 Aug 9:15353702211036055. Epub 2021 Aug 9.

Department of Cardiology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai 200135, China.

In heart failure (HF) patients with reduced ejection fraction, LIPCAR, a long noncoding RNA is elevated and is associated with left ventricular remodeling and poor prognosis. We studied the role of LIPCAR in patients with HF post-acute myocardial infarction (AMI) to find biomarkers for early detection of HF. We conducted a study of 127 patients with AMI, of which 59 were patients with HF post-AMI. LIPCAR levels were higher in HF patients post-AMI than patients without HF, and LIPCAR had a high predictive value for diagnosis of HF, which was estimated by receiver operating characteristic curves (AUC: 0.985). The results indicate that LIPCAR may be a marker of early HF after AMI.
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http://dx.doi.org/10.1177/15353702211036055DOI Listing
August 2021

Association of Bw4/Bw6 mismatch across class I HLA loci with renal graft outcomes in first time transplants.

Hum Immunol 2021 Aug 3. Epub 2021 Aug 3.

Department of Pathology and Immunology, Washington University in St Louis, MO, United States. Electronic address:

Bw4 and Bw6 are strongly immunogenic epitopes routinely assigned based on HLA-B typing results per Organ Procurement and Transplantation Network (OPTN) policies. These public epitopes and their variants are shared by some cross-reactive HLA-A and -C antigens. Although epitope mismatch has been associated with poor transplant outcomes, previous studies did not find such associations for Bw4/6 mismatch as defined by HLA-B antigens only. We hypothesized that a broader definition for Bw4/Bw6 mismatch that includes cross-reactive HLA-A and -C antigens may reveal the risk associated with these epitopes. In this retrospective cohort study, we examined kidney transplantations between 2000 and 2016 in the OPTN database and determined the association of Bw4/6 mismatch across all class I HLA antigens and renal graft outcomes. Even by this broader definition, Bw4/6 mismatch was not independently associated with 1-year graft rejection (adjusted OR: 0.99, 95%CI 0.93-1.06) or death-censored graft survival (adjusted HR: 1.02, 95%CI 1.00-1.05). There was no significant association among recipients who were already sensitized at transplant either. Our findings suggest that Bw4/6 mismatch alone is not associated with poor renal graft outcomes despite their strong immunogenicity, and the load of epitope mismatches over a certain threshold is likely required to cause adverse clinical consequences.
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http://dx.doi.org/10.1016/j.humimm.2021.07.008DOI Listing
August 2021

()-2,6,10-Trimethyldodec-8-en-2-ol: An Undescribed Sesquiterpenoid from Copaiba Oil.

Molecules 2021 Jul 23;26(15). Epub 2021 Jul 23.

Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as ()-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.
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http://dx.doi.org/10.3390/molecules26154456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348878PMC
July 2021

Inhibition of hypoxia-inducible factor-1α alleviates acinar cell necrosis in a mouse model of acute pancreatitis.

Biochem Biophys Res Commun 2021 Oct 3;572:72-79. Epub 2021 Aug 3.

Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China. Electronic address:

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.043DOI Listing
October 2021

Is intravenous iodinated contrast medium administration really harmful in hospitalized acute kidney injury patients: a propensity score-matched study.

Eur Radiol 2021 Aug 3. Epub 2021 Aug 3.

Department of Nephrology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, 139 Renmin Road, Changsha, 410011, Hunan, China.

Objectives: To evaluate the effects of intravenous iodinated contrast medium (ICM) administration on the deterioration of renal function (DRF), new renal replacement therapy (RRT) induction and mortality of hospitalized acute kidney injury (AKI) patients.

Methods: Adult hospitalized patients undergoing a contrast-enhanced or unenhanced CT scan within 7 days after AKI diagnosis from January 2015 to December 2019 were identified in this retrospective study. Propensity score matching was performed. Outcomes in 7 and 30 days after CT scan were compared between the contrast and non-contrast groups. Additional analyses were also performed in patients stratified by SCr levels at AKI diagnosis, times and time of CT scan, and in patients without chronic kidney disease or RRT requirement prior to CT scan.

Results: In total, 1172 pairs were generated after 1:1 propensity score matching from 1336 cases exposed to ICM and 2724 unexposed. No significant differences were found in the outcomes between the two groups: DRF, 7.8% vs 9.0% (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.62-1.11) in 7 days, 5.1% vs 5.4% (OR 0.93, 95%CI 0.64-1.34) in 30 days; new RRT induction, 2.3% vs 3.3% (OR 0.72,95%CI 0.43-1.18) in 7 days, 4.2% vs 4.5% (OR 0.95,95%CI 0.64-1.41) in 30 days; and mortality, 3.9% vs 4.8% (OR 0.83,95%CI 0.56-1.22) in 7 days, 9.0% vs 10.2% (OR 0.88,95%CI 0.68-1.15) in 30 days. Subset analyses showed similar results.

Conclusion: Intravenous ICM administration during AKI duration did not increase the risks of DRF, new RRT induction, and mortality in 7 and 30 days after CT scan.

Key Points: • Intravenous ICM administration in hospitalized AKI patients does not increase the risks of deterioration of renal function, RRT induction, and mortality in 7 and 30 days after CT scan. • The effects of intravenous ICM on adverse outcomes are minimal even in AKI patients with high level of SCr values or multiple CT scans.
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http://dx.doi.org/10.1007/s00330-021-08192-2DOI Listing
August 2021

The miR528- Module Confers Enhanced Salt Tolerance in Rice by Modulating the Ascorbic Acid and Abscisic Acid Metabolism and ROS Scavenging.

J Agric Food Chem 2021 Aug 2;69(31):8634-8648. Epub 2021 Aug 2.

The Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, College of Advanced Agricultural Sciences, Zhejiang A&F University, Lin'an, Hangzhou 311300, P. R. China.

The monocot lineage-specific miR528 was previously established as a multistress regulator. However, it remains largely unclear how miR528 participates in response to salinity stress in rice. Here, we show that miR528 positively regulates rice salt tolerance by down-regulating a gene encoding l-ascorbate oxidase (AO), thereby bolstering up the -mediated abscisic acid (ABA) synthesis and ROS scavenging. Overexpression of miR528 caused a substantial increase in ascorbic acid (AsA) and ABA contents but a significant reduction in ROS accumulation, resulting in the enhanced salt tolerance of rice plants. Conversely, knockdown of miR528 or overexpression of stimulated the expression of the gene, hence lowering the level of AsA, a critical antioxidant that promotes the ABA content but reduces the ROS level, and then compromising rice tolerance to salinity. Together, the findings reveal a novel mechanism of the miR528- module-mediated salt tolerance by modulating the processes of AsA and ABA metabolism as well as ROS detoxification, which adds a new regulatory role to the miR528- stress defense pathway in rice.
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http://dx.doi.org/10.1021/acs.jafc.1c01096DOI Listing
August 2021

Revealing Reactions between the Electron Beam and Nanoparticle Capping Ligands with Correlative Fluorescence and Liquid-Phase Electron Microscopy.

ACS Appl Mater Interfaces 2021 Aug 2;13(31):37553-37562. Epub 2021 Aug 2.

Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, College Park, Maryland 20742, United States.

Liquid-phase transmission electron microscopy (LP-TEM) enables real-time imaging of nanoparticle self-assembly, formation, and etching with single nanometer resolution. Despite the importance of organic nanoparticle capping ligands in these processes, the effect of electron beam irradiation on surface-bound and soluble capping ligands during LP-TEM imaging has not been investigated. Here, we use correlative LP-TEM and fluorescence microscopy (FM) to demonstrate that polymeric nanoparticle ligands undergo competing crosslinking and chain scission reactions that nonmonotonically modify ligand coverage over time. Branched polyethylenimine (BPEI)-coated silver nanoparticles were imaged with dose-controlled LP-TEM followed by labeling their primary amine groups with fluorophores to visualize the local thickness of adsorbed capping ligands. FM images showed that free ligands crosslinked in the LP-TEM image area over imaging times of tens of seconds, enhancing local capping ligand coverage on nanoparticles and silicon nitride membranes. Nanoparticle surface ligands underwent chain scission over irradiation times of minutes to tens of minutes, which depleted surface ligands from the nanoparticle and silicon nitride surface. Conversely, solutions of only soluble capping ligand underwent successive crosslinking reactions with no chain scission, suggesting that nanoparticles enhanced the chain scission reactions by acting as radiolysis hotspots. The addition of a hydroxyl radical scavenger, -butanol, eliminated chain scission reactions and slowed the progression of crosslinking reactions. These experiments have important implications for performing controlled and reproducible LP-TEM nanoparticle imaging as they demonstrate that the electron beam can significantly alter ligand coverage on nanoparticles in a nonintuitive manner. They emphasize the need to understand and control the electron beam radiation chemistry of a given sample to avoid significant perturbations to the nanoparticle capping ligand chemistry, which are invisible in electron micrographs.
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http://dx.doi.org/10.1021/acsami.1c10957DOI Listing
August 2021

All-Trans Retinoic Acid Enhances Chemosensitivity to 5-FU by Targeting miR-378c/E2F7 Axis in Colorectal Cancer.

J Oncol 2021 19;2021:5338934. Epub 2021 Jul 19.

Department of Proctology(II), Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, Shandong, China.

Colorectal carcinoma (CRC), a life-threatening malignancy, has been found to present resistance to 5-fluorouracil (5-FU) and cause a poor prognosis for patients. Previous studies have proved that all-trans retinoic acid (ATRA) could inhibit the development of CRC cells. In addition, miR-378c was discovered to exert a vital role in various cancers. In this study, we utilized MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), transwell assay, and flow cytometry to confirm that ATRA was able to enhance the inhibitory effects of 5-FU on HCT116 cells effectively by promoting cell apoptosis. Then, ENCORI database (http://starbase.sysu.edu.cn/) was employed to predict that miR-378c was downregulated dramatically in CRC and E2F7 was the direct target of miR-378c. QRT-PCR (quantitative real-time polymerase chain reaction) was conducted to verify that the expression level of miR-378c was decreased while E2F7 expression was upregulated in CRC tissues compared with para-carcinoma tissues. Additionally, treatment of 5-FU combined with ATRA could increase miR-378c expression, whereas it decreased the expression of E2F7. Dual-Luciferase Reporter assay results revealed that miR-378c could regulate the load of E2F7 by binding to its 3'UTR directly. Furthermore, miR-378c inhibitor or vector with E2F7 partially counteracted the effects of 5-FU combined with ATRA on viability, migration, invasion, and apoptosis of HCT116 cells. In conclusion, our study aims to confirm that ATRA enhances chemosensitivity to 5-FU of patients with CRC and expound the potential molecular mechanisms.
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http://dx.doi.org/10.1155/2021/5338934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318767PMC
July 2021

CellCall: integrating paired ligand-receptor and transcription factor activities for cell-cell communication.

Nucleic Acids Res 2021 Sep;49(15):8520-8534

State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

With the dramatic development of single-cell RNA sequencing (scRNA-seq) technologies, the systematic decoding of cell-cell communication has received great research interest. To date, several in-silico methods have been developed, but most of them lack the ability to predict the communication pathways connecting the insides and outsides of cells. Here, we developed CellCall, a toolkit to infer inter- and intracellular communication pathways by integrating paired ligand-receptor and transcription factor (TF) activity. Moreover, CellCall uses an embedded pathway activity analysis method to identify the significantly activated pathways involved in intercellular crosstalk between certain cell types. Additionally, CellCall offers a rich suite of visualization options (Circos plot, Sankey plot, bubble plot, ridge plot, etc.) to present the analysis results. Case studies on scRNA-seq datasets of human testicular cells and the tumor immune microenvironment demonstrated the reliable and unique functionality of CellCall in intercellular communication analysis and internal TF activity exploration, which were further validated experimentally. Comparative analysis of CellCall and other tools indicated that CellCall was more accurate and offered more functions. In summary, CellCall provides a sophisticated and practical tool allowing researchers to decipher intercellular communication and related internal regulatory signals based on scRNA-seq data. CellCall is freely available at https://github.com/ShellyCoder/cellcall.
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http://dx.doi.org/10.1093/nar/gkab638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421219PMC
September 2021

pH-Mediated Aggregation-to-Separation Transition for Colloids Near Electrodes in Oscillatory Electric Fields.

Langmuir 2021 Aug 29;37(31):9346-9355. Epub 2021 Jul 29.

Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 21044, United States.

Colloids in low-frequency (<1 kHz) oscillatory electric fields near planar electrodes aggregate in neutral pH electrolytes due to electrohydrodynamic (EHD) flow but separate in alkaline pH electrolytes. Colloid ζ-potential and electrolyte ion mobilities are thought to play roles in the underlying mechanism for this phenomenon, but a unifying theory for why particles aggregate in some electrolytes and separate in others remains to be established. Here, we show that increasing local pH near the electrode with an electrochemical reaction causes a colloidal aggregation-to-separation transition in oscillatory electric fields that induce strong attractive EHD flows. An electroactive molecule, -benzoquinone, was electrochemically reduced at the electrode to locally increase the solution pH near the colloids. Superimposing a sufficiently large steady electrochemical potential onto an oscillatory potential caused a reversible aggregation-to-separation transition. Counterintuitively, decreasing frequency, which increases attractive EHD drag forces, caused a similar aggregation-to-separation transition. Even more interesting, multiple transitions were observed while varying the oscillatory potential. Taken together, these results suggested that the oscillatory potential induced a repulsive hydrodynamic drag force. Scaling arguments for the recently discovered asymmetric rectified electric field (AREF) showed that a repulsive AREF-induced electroosmotic (EO) flow competed with attractive EHD flow. A pairwise colloidal force balance including these competing flows exhibited flow inversions qualitatively consistent with experimentally observed aggregation-to-separation transitions. Broadly, these results emphasize the importance of AREF-induced EO flows in colloid aggregation and separation in low-frequency oscillatory electric fields.
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http://dx.doi.org/10.1021/acs.langmuir.1c00671DOI Listing
August 2021

Development of mortality prediction model in the elderly hospitalized AKI patients.

Sci Rep 2021 Jul 26;11(1):15157. Epub 2021 Jul 26.

Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.

Acute kidney injury (AKI) correlates with increased health-care costs and poor outcomes in older adults. However, there is no good scoring system to predict mortality within 30-day, 1-year after AKI in older adults. We performed a retrospective analysis screening data of 53,944 hospitalized elderly patients (age > 65 years) from multi-centers in China. 944 patients with AKI (acute kidney disease) were included and followed up for 1 year. Multivariable regression analysis was used for developing scoring models in the test group (a randomly 70% of all the patients). The established models have been verified in the validation group (a randomly 30% of all the patients). Model 1 that consisted of the risk factors for death within 30 days after AKI had accurate discrimination (The area under the receiver operating characteristic curves, AUROC: 0.90 (95% CI 0.875-0.932)) in the test group, and performed well in the validation groups (AUROC: 0.907 (95% CI 0.865-0.949)). The scoring formula of all-cause death within 1 year (model 2) is a seven-variable model including AKI type, solid tumor, renal replacement therapy, acute myocardial infarction, mechanical ventilation, the number of organ failures, and proteinuria. The area under the receiver operating characteristic (AUROC) curves of model 2 was > 0.80 both in the test and validation groups. Our newly established risk models can well predict the risk of all-cause death in older hospitalized AKI patients within 30 days or 1 year.
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http://dx.doi.org/10.1038/s41598-021-94271-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313696PMC
July 2021

Early diagnosis, treatment, and outcomes of five patients with acute thallium poisoning.

World J Clin Cases 2021 Jul;9(19):5082-5091

Department of Geriatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China.

Background: Thallium poisoning is rare and difficult to recognize. Early diagnosis and treatment of thallium-poisoned patients are essential to prevent morbidity and mortality.

Aim: To evaluate the efficacy of treatments and outcomes of five patients with early diagnosis of acute thallium poisoning.

Methods: Five patients who consumed a thallium-contaminated meal were hospitalized in succession, and underwent clinical examinations such as blood tests and electromyography tests. Urine and blood tests confirmed the diagnosis of thallotoxicosis, revealing the occurrence of food poisoning. All patients underwent detoxification treatment, including hemoperfusion (HP) and treatment with Prussian blue (PB). A 24-mo follow-up was performed to evaluate the long-term outcomes on the patients after discharge.

Results: Initially, the patients presented with symptoms of acute thallium poisoning including hyperalgesia of the limbs and abdominalgia, which may differ from common peripheral neuropathy. Accompanying symptoms such as hepatic damage and alopecia were observed in all the patients, which further confirmed the diagnosis of poisoning. Treatment with chelating agents was ineffective, while HP and treatment with PB drastically decreased the thallium concentration in the urine and blood. With early diagnosis and intervention, four patients had a good prognosis and no permanent sequelae. One patient developed blindness and disability during the 24-mo follow-up period.

Conclusion: Identification of incident cluster and characteristic symptoms is extremely important for early diagnosis of acute thallium poisoning. HP plus PB is essential to improve the prognosis of thallium-poisoned patients.
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http://dx.doi.org/10.12998/wjcc.v9.i19.5082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283604PMC
July 2021

Case Report: Prenatal and Postnatal Management for Fetal Bronchogenic Cysts During the COVID-19 Pandemic.

Front Pediatr 2021 7;9:675883. Epub 2021 Jul 7.

Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, China.

A fetal bronchogenic cyst (BC) is a rare congenital anomaly with an incidence of 0.147-0.238‰. The coronavirus disease 2019 (COVID-19) pandemic, as a particular situation, hindered pregnant women from receiving periodic prenatal checkups. Until 34 weeks of gestation, a fetal case of the intrathoracic cyst was found by ultrasound examination. Further, MRI examination confirmed the diagnosis of the congenital mediastinal cystic lesion, probably a BC. Genetic testing was not conducted due to the COVID-19 pandemic. At 38 weeks of gestation with maternal COVID-19 testing negative, a live girl was delivered by cesarean section. Five months later, the child underwent bronchocystectomy, and the postoperative pathological lesions confirmed a (right upper mediastinum) BC. Herein, we reported the prenatal and postnatal management for a rare case of the congenital BC by multidisciplinary approaches during the COVID-19 pandemic. Fetal MRI and screening for fetal chromosomal abnormalities are especially recommended. This case contributes to the awareness that the COVID-19 pandemic interferes with regular follow-up schedules during pregnancy and may interfere with timely performed additional tests; which leads to more accurate genetic counseling. A combination of multidisciplinary approaches, including radiology, infection control, genetic counseling, obstetrics, and pediatric surgery, is pivotal for managing fetal BC during the COVID-19 pandemic.
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http://dx.doi.org/10.3389/fped.2021.675883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292643PMC
July 2021

Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth.

Stem Cells Int 2021 29;2021:9989790. Epub 2021 Jun 29.

School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy.
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http://dx.doi.org/10.1155/2021/9989790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263240PMC
June 2021

Changes in Chinese Adults' Physical Activity Behavior and Determinants before and during the COVID-19 Pandemic.

J Clin Med 2021 Jul 11;10(14). Epub 2021 Jul 11.

School of Kinesiology, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA.

Purpose: To investigate the changes in Chinese adults' physical activity (PA) behavior and determinants before and during the COVID-19 pandemic.

Method: A total of 1028 adults (aged 19-59 years) were recruited from 127 urban and rural neighborhoods in China using stratified three-stage probability sampling. Data collection was conducted in December 2019 and July 2020.

Results: Compared with the data before the pandemic, individuals' weekly moderate-to-vigorous-intensity PA (MVPA) decreased significantly from 139 min to 120 min, seven months after the outbreak ( 0.01), with female and rural populations displaying a more significant decrease ( 0.02). Overall, 13.7% of participants met the PA guidelines (World Health Organization) both before and during the pandemic, while 21.8% met the guidelines only before the pandemic and 18.1% increased their PA and met the PA guidelines during the pandemic. A total of 46.4% did not meet the PA guidelines before or during the pandemic. Determinants of PA behavior change before and during the pandemic included sports skills, self-determined motivation and support from sports organizations.

Conclusions: The Chinese adults' PA levels decreased significantly from before to during the COVID-19 pandemic, particularly among the female population. It is suggested that the enhancement of self-determined motivation, improvement of sport skills, and support from sports organizations might be effective in facilitating individuals' engagement in PA during the pandemic.
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http://dx.doi.org/10.3390/jcm10143069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303329PMC
July 2021

Cepharanthine sensitizes human triple negative breast cancer cells to chemotherapeutic agent epirubicin via inducing cofilin oxidation-mediated mitochondrial fission and apoptosis.

Acta Pharmacol Sin 2021 Jul 22. Epub 2021 Jul 22.

Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563006, China.

Inhibition of autophagy has been accepted as a promising therapeutic strategy in cancer, but its clinical application is hindered by lack of effective and specific autophagy inhibitors. We previously identified cepharanthine (CEP) as a novel autophagy inhibitor, which inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. In this study we investigated whether and how inhibition of autophagy/mitophagy by cepharanthine affected the efficacy of chemotherapeutic agent epirubicin in triple negative breast cancer (TNBC) cells in vitro and in vivo. In human breast cancer MDA-MB-231 and BT549 cells, application of CEP (2 μM) greatly enhanced cepharanthine-induced inhibition on cell viability and colony formation. CEP interacted with epirubicin synergistically to induce apoptosis in TNBC cells via the mitochondrial pathway. We demonstrated that co-administration of CEP and epirubicin induced mitochondrial fission in MDA-MB-231 cells, and the production of mitochondrial superoxide was correlated with mitochondrial fission and apoptosis induced by the combination. Moreover, we revealed that co-administration of CEP and epirubicin markedly increased the generation of mitochondrial superoxide, resulting in oxidation of the actin-remodeling protein cofilin, which promoted formation of an intramolecular disulfide bridge between Cys39 and Cys80 as well as Ser3 dephosphorylation, leading to mitochondria translocation of cofilin, thus causing mitochondrial fission and apoptosis. Finally, in mice bearing MDA-MB-231 cell xenografts, co-administration of CEP (12 mg/kg, ip, once every other day for 36 days) greatly enhanced the therapeutic efficacy of epirubicin (2 mg/kg) as compared with administration of either drug alone. Taken together, our results implicate that a combination of cepharanthine with chemotherapeutic agents could represent a novel therapeutic strategy for the treatment of breast cancer.
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http://dx.doi.org/10.1038/s41401-021-00715-3DOI Listing
July 2021
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