Publications by authors named "Jin Zhao"

947 Publications

Evaluating source-oriented human health risk of potentially toxic elements: A new exploration of multiple age groups division.

Authors:
Zhao Jin Jianshu Lv

Sci Total Environ 2021 May 4;787:147502. Epub 2021 May 4.

College of Geography and Environment, Shandong Normal University, Ji'nan 250014, China. Electronic address:

Effective source-oriented human health risk assessment (HHRA) for people in different life stages will guide pollution control and risk prevention. This work integrated three receptor models of positive matrix factorization, Unmix, and factor analysis with nonnegative constraints for accurate source-oriented HHRA of potentially toxic elements in 6 age groups of populations (0-<1 year, 1-<6 years, 6-<12 years, 12-<18 years, 18-<44 years, and 44+ years). Four sources were identified. Natural source controlled As, Cr, and Ni in dust and soil as well as Pb and Zn in soil. Industrial-traffic emissions contributed most of Cd in dust and soil as well as Pb and Zn in dust. Hg in both dust and soil originated from coal combustion. Construction works contributed more to PTEs in soil than in dust. Noncarcinogenic and carcinogenic risk for both dust and soil changed in similar trends by age. The noncancer risk reduced with increasing age for people below 44 years. Carcinogenic risk of females over 44 years were the highest, while children from 0 to 1 year faced the lowest carcinogenic risk. Among the four origins of PTEs, natural sources contributed most to health risk of PTEs, followed by industrial-traffic sources, construction works, and coal combustion. Based on sequential Gaussian simulation (SGS), the susceptible population and risk areas were identified. Children from 0 to 6 years were identified as susceptible population. The areas with noncancer risk in dust were 19.15 km for 0-<1 year and 3.14 km for children from 1 to <6 years, and noncancer risk areas in soil were 30.26 km for 0-<1 year and 0.85 km for 1-<6 years. Relevant control and management works were demanded on children from 0 to 6 years and noncancer risk areas.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147502DOI Listing
May 2021

A Case of Phyllodes Tumor of the Breast with Mixed Liposarcoma: Case Report and Literature Review.

Onco Targets Ther 2021 6;14:3003-3011. Epub 2021 May 6.

Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, People's Republic of China.

Phyllodes tumors (PTs) account for less than 1% of breast tumors, and malignant PTs account for even less. Here, we described an unusual case of malignant PT with mixed liposarcoma (myxoid liposarcoma [MLP] and pleomorphic liposarcoma [PLP]). A 52-year-old woman discovered a small lump in her left breast. Twenty years later, the lump suddenly grew within 1 month. Mammography showed space-occupying lesions of the left breast. Histologically, the tumor was characterized by hypercellular stroma covering the epithelium and protrusion of the myoepithelium into the cyst to form a lobulated structure; regions of loose mucus and hypercellular structures alternated. A region of peripheral benign fibroadenoma was also observed, and many stellate and spindle cells or signet ring-like cells were identified in loose areas. Some areas showed a characteristic thin branching vascular pattern. In the cell-rich area, adipocytes and odd megakaryocytes were observed. Atypical mitotic figures were observed in the cell-rich and mucus areas (16 mitoses/10 high-power fields [HPF] and 2 mitoses/10 HPF, respectively). In the immunohistochemical analysis, a small number of tumor cells were positive for AE1/3 and vimentin, whereas all cells were negative for cytokeratin 34βE12, E-cadherin, p63, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and S-100, ruling out the possibility of metaplastic carcinoma. Interestingly, cyclin-dependent kinase 4, mouse double minute 2 (MDM2), and p16 were strongly positive in both loose mucus and cell-rich areas. However, the fluorescence in situ hybridization test results showed that MDM2 was not amplified. Combined with morphological characteristics, these findings supported that the tumor was a mixed malignant PT with MLP and PLP. Our patient did not receive radiation therapy, and after 47 months of follow-up, no recurrence or metastasis occurred. This case report serves to expand the morphologic spectrum of mixed malignant PT with liposarcoma.
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http://dx.doi.org/10.2147/OTT.S298379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110257PMC
May 2021

HIV-1 Infection Alters the Viral Composition of Plasma in Men Who Have Sex with Men.

mSphere 2021 May 5;6(3). Epub 2021 May 5.

Shanghai Clinical Research Center for Infectious Disease (HIV/AIDS), Shanghai Public Health Clinical Center, Fudan University, Shanghai, China

Altered gut virome and expanded abundance of certain viruses were found in HIV-1-infected individuals. It remains largely unknown how plasma virus composition changes during HIV-1 infection and antiretroviral therapy (ART). We performed viral metagenomic analysis on viral particles enriched from human plasma from 101 men who have sex with men (MSM) with or without HIV-1 infection and whether or not on ART and compared the differences in the plasma virome. An increased plasma viral abundance of main eukaryotic viruses was observed during HIV-1 infection in MSM, especially in AIDS patients (CD4 T cell counts of <200). Anellovirus, pegivirus and hepatitis B virus (HBV) were the most abundant blood-borne viruses detected among MSM and HIV-1-infected individuals, and anellovirus and pegivirus were closely related to HIV-1 infection. High diversity of anelloviruses was found mostly in HIV-1-infected MSM, and their abundance was positively correlated with the HIV-1 viral load, but negatively correlated with both CD4 T cell counts and CD4/CD8 ratio; in contrast, the abundance of pegivirus showed opposite correlations. ART usage could restore the plasma virome toward that of HIV-1-negative individuals. These data showed an expansion in abundance of certain viruses during HIV-1 infection, indicating the higher risk of shedding some blood-borne viruses in these individuals. These investigations indicate that both anellovirus and pegivirus may play certain roles in HIV disease progression. Though an increasing number of studies have indicated the existence of an interaction between the virome and human health or disease, the specific role of these plasma viral components remains largely unsolved. We provide evidence here that an altered plasma virome profile is associated with different immune status of HIV-1 infection. Specific resident viruses, such as anellovirus and pegivirus, may directly or indirectly participate in the disease progression of HIV-1 infection. These results can help to determine their clinical relevance and design potential therapies.
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http://dx.doi.org/10.1128/mSphere.00081-21DOI Listing
May 2021

Phosphatidylcholine-Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery.

Macromol Biosci 2021 May 5:e2100042. Epub 2021 May 5.

Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China.

Exosomes derived from non-tumor cells hold great potential as drug delivery vehicles because of their good biosafety and natural transference of bioactive cargo between cells. However, compared to tumor-derived exosomes, efficient delivery is limited by their weak interactions with tumor cells. It is essential to engineer exosomes that improve tumor cellular internalization efficiency. A simple and effective strategy to enhance tumor cell uptake by engineering the exosome membrane lipids can be established by drawing on the role of lipids in tumor exosomes interacting with tumor cells. Amphiphilic phosphatidylcholine (PC) molecules are inserted into the membrane lipid layer of reticulocyte-derived exosomes (Exos) by simple incubation to construct PC-engineered exosomes (PC-Exos). It is demonstrated that PC-Exos showed significantly enhanced tumor cell internalization and uptake rate compared to native Exos, up to a twofold increase. After therapeutic agent loading, PC-Exos remarkably promotes intracellular drug or RNA accumulation in cancer cells, thus showing enhanced in vitro anti-tumor activity. This work demonstrates the crucial role of engineering exosomal lipids in modulating cancer cellular uptake, which may shed light on the design of high-efficiency exosome-based drug delivery carriers.
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http://dx.doi.org/10.1002/mabi.202100042DOI Listing
May 2021

Evaluation of the Genetic Association and Methylation of Immune Response Pathway Genes with the Risk of Chronic Periodontitis in the Uighur Population.

Genet Test Mol Biomarkers 2021 May 4. Epub 2021 May 4.

Department of Endodontics, First Affiliated Hospital of Xinjiang Medical University, and College of Stomatology of Xinjiang Medical University, Urumqi, China.

The aim of this study was to explore the possible associations between single nucleotide polymorphisms (SNPs) and DNA methylation levels of seven genes in the inflammatory response pathway with susceptibility to chronic periodontitis (CP) among the Uighur population of the Xinjiang Autonomous Region of China. A total of 444 eligible subjects (279 CP patients and 165 healthy controls) were enrolled in the study. Genomic DNA was obtained from gingival tissue for genotyping eight SNPs and performing methylation measurements of seven genes. SNP in the formyl peptide receptor 1 () gene achieved statistical significance in the standard allelic association analysis for CP ( = 0.02). The frequency of the minor allele G was higher in the cases than in controls (0.367 vs. 0.291). Additionally, was significantly associated with CP under the dominant genetic model ( = 0.03). Using logistic regression analysis, was found to be consistently associated with CP under the additive dominant model, and this association remained significant after covariates were taken into account [odds ratio (OR) = 1.49 (1.09-2.05),  = 0.014; OR = 1.58 (1.04-2.40),  = 0.031, respectively]. No significant gene-gene interactions were identified. Although we did not find a polymorphism in interleukin 6 () associated with CP in our study, the methylation level of a CpG island region located within the promoter region of was significantly less in CP patients compared with controls ( < 0.05). The genetic polymorphism in and the methylation level of the promoter region of might be associated with CP in the Uighur population of China.
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http://dx.doi.org/10.1089/gtmb.2020.0334DOI Listing
May 2021

Theoretical study on water behavior on the copper surfaces.

J Mol Model 2021 May 3;27(5):149. Epub 2021 May 3.

College of Chemistry and Chemical Engineering, Yantai University, Yantai, 264005, People's Republic of China.

We calculated the adsorption of H, O, OH, and HO and the dissociation of HO molecule on the Cu(111), Cu(100), and Cu(110) surfaces using density functional theory. H, O, and OH tend to adsorb stably at the highly coordinated dh and h sites on the Cu(111) and Cu(100) surfaces. OH and H tend to adsorb on sb site on the Cu(110) surface. The more charge transfer of the adsorbed substance, the more stable the adsorption. The dissociation product is O+H on the Cu(111) surface, while the dissociation product is OH+H on the Cu(100) and Cu(110) surfaces. Due to the different geometric structures of initial state (IS), transition state (TS), and final state (FS) in the dissociation reaction, the dissociation of water on the copper surface does not establish a linear Brønsted-Evans-Polanyi (BEP) relationship. These results provide theoretical support for the understanding of the interaction between water and metals as well as the behavior of water molecules.
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http://dx.doi.org/10.1007/s00894-021-04751-yDOI Listing
May 2021

Association between medical male circumcision and HIV risk compensation among heterosexual men: a systematic review and meta-analysis.

Lancet Glob Health 2021 Apr 30. Epub 2021 Apr 30.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China; Kirby Institute, University of New South Wales, Sydney, NSW, Australia; School of Public Health, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: Medical male circumcision (MMC) reduces HIV infection among heterosexual men. There are concerns MMC might prompt higher-risk sexual behaviours because of lower self-perceived risk of HIV infection. We reviewed the published literature to examine associations between MMC and both condom use and number of sex partners among heterosexual men.

Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library for studies published before Nov 15, 2020. Interventional and observational studies were included if they contained original quantitative data describing the association between MMC and condom use or number of sex partners among heterosexual men. We excluded data from men whose circumcisions were ritual or religious and data from men who have sex with men. We extracted odds ratios (ORs) and 95% CIs for the associations between MMC and condomless sex and MMC and multiple sex partners directly from the publications if available, selecting adjusted ORs when provided; when necessary, we calculated ORs and 95% CIs using original study data provided in the publication. We used the Mantel-Haenszel random effects model to calculate pooled ORs and 95% CIs.

Findings: Our search yielded 3035 results, of which 471 were duplicates and 2537 did not meet the inclusion criteria. From the remaining 27 eligible studies, we identified 99 292 men from 31 independent population samples. 24 studies were done in Africa. We found no statistically significant associations between MMC and condomless sex (OR 0·91, 95% CI 0·80-1·05; k=30; I=88·7%) or multiple sex partners (1·02, 0·88-1·18; k=27; I=90·1%). No associations between MMC and condomless sex or multiple sexual partners were found in any subgroup analyses by study design, income of country, age, recruitment setting, circumcision assessment, circumcision prevalence, and risk of publication bias.

Interpretation: The promotion of circumcision as an HIV preventive measure does not appear to increase higher-risk sexual behaviours in heterosexual men. Ongoing sexual health education should be maintained as a vital component of effective MMC programmes.

Funding: National Science and Technology Major Project of China, the Fundamental Research Funds for the Central Universities, and the Shenzhen Science and Technology Innovation Commission Basic Research Program.
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http://dx.doi.org/10.1016/S2214-109X(21)00102-9DOI Listing
April 2021

Identification of TAPBPL as a novel negative regulator of T-cell function.

EMBO Mol Med 2021 May 3;13(5):e13404. Epub 2021 May 3.

Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.

T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co-inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. The putative TAPBPL receptor is expressed on activated CD4 and CD8 T cells. A soluble recombinant human TAPBPL-IgG Fc (hTAPBPL-Ig) fusion protein inhibits the proliferation, activation, and cytokine production of both mouse and human T cells in vitro. In vivo administration of hTAPBPL-Ig protein attenuates experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, an anti-TAPBPL monoclonal antibody neutralizes the inhibitory activity of hTAPBPL-Ig on T cells, enhances antitumor immunity, and inhibits tumor growth in animal models. Our results suggest that therapeutic intervention of the TAPBPL inhibitory pathway may represent a new strategy to modulate T cell-mediated immunity for the treatment of cancer, infections, autoimmune diseases, and transplant rejection.
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http://dx.doi.org/10.15252/emmm.202013404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103088PMC
May 2021

Grandparental care and sleep disturbances in preschool children: a population-based prospective cohort study.

Sleep Med 2021 Apr 10;82:165-171. Epub 2021 Apr 10.

Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai, China; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objectives: Sleep disturbances are common in preschoolers, and profoundly affected by parenting. Grandparents are increasingly involved in childcare and have attracted worldwide attention for their potential impacts on child well-being. However, no studies have explored child sleep health within the context of grandparental care. We aimed to explore the association between grandparents as primary caregivers and children's sleep disturbances.

Methods: Participants included 20,324 preschoolers from the Shanghai Children's Health, Education and Lifestyle Evaluation-Preschool (SCHEDULE-P) in Shanghai, China. They were initially assessed in November 2016 and were reassessed in April 2018 and April 2019. Children's primary caregivers were collected at each survey. Sleep disturbances were assessed by the Children's Sleep Habits Questionnaire (CSHQ).

Results: At baseline, 84.4% of children had global sleep disturbances (CSHQ total score >41). Compared with parents, random-effects model indicated that grandparents as primary caregivers increased the adjusted odds ratio (OR) for children's global sleep disturbances by 30% (OR [95%CI]: 1.30 [1.21, 1.40]). To the specific domains of CSHQ, two-way repeated-measures ANOVA showed significant "caregiver transition" group × wave interaction in the behavioral sleep disturbances, such as "Bedtime Resistance" (p < 0.001). At each survey, children with grandparents as primary caregivers demonstrated significant higher behavioral sleep disturbances than their counterparts with parental care.

Conclusions: Grandparental care is associated with increased sleep disturbances, particularly behavioral sleep disturbances, in preschoolers. Future studies should explore the underlying mechanisms and whether sleep programs targeting grandparents can decrease children's sleep disturbances.
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http://dx.doi.org/10.1016/j.sleep.2021.03.033DOI Listing
April 2021

Molecular surveillance of HIV-1 newly diagnosed infections in Shenzhen, China from 2011 to 2018.

J Infect 2021 Apr 28. Epub 2021 Apr 28.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. Electronic address:

Objectives: Shenzhen is suffering severe HIV epidemic. No systematic surveillance on high risk populations, HIV genetic diversity, transmitted drug resistance (TDR) and molecular transmission clusters (MTCs) have been reported yet. In this study, we described them based on newly diagnosed HIV positive cases from 2011 to 2018 in Shenzhen city, China.

Methods: Plasma samples of newly reported HIV positive cases in Shenzhen, China were collected from 2011 to 2018. The HIV pol gene was amplified and sequenced for subtyping, genetic characterization, TDR and phylogenetic analysis. Demographic and risk characteristics associated with transmitted drug resistance-associated mutations (TDRAMs) and MTCs were explored by using logistic regression analyses.

Results: 10378 HIV pol sequences were successfully obtained from newly diagnosed patients with available background information. The most prevalent HIV-1 subtype was CRF07_BC (40.92%). CRF07_BC, CRF55_01B and URFs increased across years. Total TDR was 6.02% during 2011 to 2018. CRF01_AE, CRF08_BC, CRF55_01B and subtype B were more likely to be associated with TDRAMs than CRF07_BC. 4460 (42.98%) patients were infected with strains included in MTCs. Patients younger than 30 and over 50 years were more likely to cluster.

Conclusions: The prevalence of HIV-1 drug resistance and molecular transmission clusters in Shenzhen should raise a high alert. Interventions targeting on patients with strains locating in MTCs should be considered to improve prevention effect in Shenzhen.
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http://dx.doi.org/10.1016/j.jinf.2021.04.021DOI Listing
April 2021

Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 514400, China.

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that , as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-β production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases.
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http://dx.doi.org/10.3390/ijms22094668DOI Listing
April 2021

Acceptability of male circumcision for HIV prevention among men who have sex with men in China: a short report.

AIDS Care 2021 Apr 28:1-8. Epub 2021 Apr 28.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China.

Recent evidence shows that circumcision is associated with lower HIV prevalence among MSM. We assessed the acceptability of circumcision for preventing HIV and that of Shang Ring circumcision (SRC) among men who have sex with men (MSM) in China. 538 adult MSM were recruited from six cities in China between January and March 2019. Participants were surveyed by an online, self-administered questionnaire. The acceptability of circumcision was assessed before and after the potential protective effect of circumcision against HIV was informed, and subsequently men's willingness to undergo SRC was assessed. The level of circumcision was 16.4%. Of 450 uncircumcised MSM, their willingness to be circumcised in the following six months increased significantly from 32.2% to 55.6% after the information session. Three quarters of men who were willing to undergo circumcision accepted SRC. MSM who perceived that circumcision could maintain genital hygiene were more likely to accept circumcision after the information session, whereas those who regarded circumcision as an embarrassing surgery were disinclined to be circumcised. The low circumcision rate, along with its high acceptability in Chinese MSM, suggests a great potential benefit of circumcision intervention if proved effective. SRC might be a popular circumcision procedure in this population.
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http://dx.doi.org/10.1080/09540121.2021.1917759DOI Listing
April 2021

Cyanidin-3-O-glucoside and cisplatin inhibit proliferation and downregulate the PI3K/AKT/mTOR pathway in cervical cancer cells.

J Food Sci 2021 Apr 28. Epub 2021 Apr 28.

College of Food Science, Shenyang Agricultural University, Shenyang, China.

Natural compounds have been increasingly investigated as substances enhancing the effect of drugs and reducing drug-related adverse reactions. The objective of this study was to determine how a combination of cisplatin (DDP) with cyanidin-3-O-glucoside (C3G) affected malignancy features of cervical cancer cells. The results demonstrated that the proliferation of HeLa cells treated with 5 µg/ml DDP, 400 µg/ml C3G, or a combination of both (5 µg/ml DDP and 400 µg/ml C3G) was inhibited by 17.43%, 34.98%, and 63.38%, respectively. The IC values for DDP and the DDP/C3G combination treatments in HeLa cells were 18.53 and 6.435 µg/ml, respectively. Flow cytometry analysis indicated that treatment with DDP, C3G, or the combination induced G1 cell cycle arrest and apoptosis in HeLa cells. Furthermore, after treatment, cyclin D1 and Bcl-2 levels decreased; Bax, cleaved caspase-3, p53, and TIMP-1 were activated; and the PI3K/AKT/mTOR signaling pathway was modulated. These anticancer effects were enhanced in cells treated with the combination of DDP and C3G compared to those treated with DDP or C3G alone. Our study indicates that C3G increases the antitumor activity of DDP, suggesting a potential strategy to reduce adverse effects associated with chemotherapy in cervical cancer. PRACTICAL APPLICATION: Natural biologically active food ingredients are suggested to have a potential to enhance the effect of chemotherapy in cancer. We believe that our study makes a significant contribution to the literature because it revealed, for the first time, that C3G could increase the antitumor activity of DDP, suggesting a potential strategy to reduce adverse effects associated with chemotherapy in cervical cancer.
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http://dx.doi.org/10.1111/1750-3841.15740DOI Listing
April 2021

Dietary flavonoid intake and risk of esophageal squamous cell carcinoma: A population-based case-control study.

Nutrition 2021 Mar 7;89:111235. Epub 2021 Mar 7.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China. Electronic address:

Objectives: The aim of this population-based case-control study was to investigate the association between dietary consumption of the total flavonoids, subclasses, and specific flavonoids and the risk of esophageal squamous cell carcinoma (ESCC) among adults in a high-risk area of China.

Methods: We recruited 820 ESCC participants and 863 control participants from Yanting County. Dietary flavonoids were assessed using a validated 76-item food frequency questionnaire. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression after considering potential confounders.

Results: Comparing the highest and lowest intake quartiles, we observed a negative association of ESCC risk with consumption of isoflavones (OR = 0.34, 95% CI = 0.23-0.50, P for trend < 0.001), daidzein (OR = 0.31, 95% CI = 0.21-0.45, P for trend < 0.001), genistein (OR = 0.34, 95% CI = 0.23-0.50, P for trend < 0.001), and glycitein (OR = 0.32, 95% CI = 0.22-0.48, P for trend < 0.001) after adjustment for potential confounders. A more pronounced negative association was observed when comparing the third quartile, rather than the fourth, with the lowest quartile for consumption of anthocyanidins (OR = 0.58, 95% CI = 0.42-0.80, P for trend = 0.004), delphinidin (OR = 0.57, 95% CI = 0.41-0.78, P for trend = 0.004), and cyanidin (OR = 0.48, 95% CI = 0.35-0.66, P for trend = 0.003) after considering potential confounders. Consumption of total flavonoids, flavones, flavonols, and six other specific flavonoids (quercetin, myricetin, kaempferol, luteolin, apigenin, and peonidin) was not associated with ESCC risk.

Conclusions: The results suggest that increased dietary intake of isoflavones and moderate consumption of anthocyanidins were associated with a decreased risk of ESCC. Future nutritional guidelines may emphasize foods or supplements rich in specific isoflavones and anthocyanidins for ESCC chemoprevention.
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http://dx.doi.org/10.1016/j.nut.2021.111235DOI Listing
March 2021

Lianhuaqingwen capsule inhibits influenza-induced bacterial adhesion to respiratory epithelial cells through down-regulation of cell adhesion molecules.

J Ethnopharmacol 2021 Apr 16:114128. Epub 2021 Apr 16.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, PR China; Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, PR China. Electronic address:

Ethnopharmacological Relevance: Influenza virus infection is widely believed to cause mild symptoms, but can lead to high mortality and severe disease complicated by secondary bacterial pneumonia. Traditional Chinese medicine (TCM) has been proposed as a promising agent to treat respiratory viral infections. An herbal formula Lianhuaqingwen capsule (LHQW) comprising two prescriptions: Maxing Shigan decoction and Yinqiao San, has been used clinically to treat respiratory infection with immune regulatory effects. However, little is known about the capacity of LHQW against influenza-induced secondary bacterial pneumonia.

Aim Of Study: This study aimed to evaluate the efficacy and underlying mechanism of LHQW on influenza A virus A/PR/8/34 (PR8) secondary methicillin-resistant Staphy-lococcus aureus (MRSA) infection.

Methods: The anti-adhesion activity of LHQW against PR8-induced MRSA infection was assessed in human lung epithelial (A549) cells and the effect of LHQW on the expression of intracellular adhesion molecule 1 (ICAM-1) was detected. Also, the mRNA expression levels of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation in PR8-infected A549 cells were determined. The body weight change, survivals, viral titers, colonies and the pathological parameters after LHQW treatment in severe pneumonia model have all been systematically determined.

Results: LHQW significantly reduced the adhesion of MRSA to PR8-infected A549 cells in a dose-dependent manner by suppressing the up-regulation of bacterial receptors. LHQW also markedly declined the overexpression of IL-6, IL-8, and TNF-α induced by LPS stimulated-A549 cells following influenza virus infection. Furthermore, the abnormal changes of lung index in dual-infection mice were relieved after administered with LHQW in preventive and therapeutic mode, but with no significantly difference (P>0.05). LHQW could not effectively improve survival rate or prolong the survival time of mice (P>0.05). LHQW (1000 mg/kg/d) administered prophylactically significantly decreased the lung viral titers (P<0.05), slightly downregulated IL-6 but TNF-α, IL-1β levels and improved lung pathological inflammation including neutrophil infiltration, necrosis, which is consistent with the expression of inflammatory factors.

Conclusions: LHQW inhibited influenza-induced bacterial adhesion by down-regulating the adhesion molecules with the improvement trend on severe pneumonia, indicating that it can be used as an adjuvant medication in severe viral-bacterial pneumonia therapy rather than as a single medication.
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http://dx.doi.org/10.1016/j.jep.2021.114128DOI Listing
April 2021

Strong Modulation of Band Gap, Carrier Mobility and Lifetime in Two-Dimensional Black Phosphorene through Acoustic Phonon Excitation.

J Phys Chem Lett 2021 Apr 19;12(16):3960-3967. Epub 2021 Apr 19.

ICQD/Hefei National Laboratory for Physical Sciences at the Microscale, and CAS Key Laboratory of Strongly-Coupled Quantum Matter Physics, and Department of Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

Black phosphorene (BP) has been attracting intense attention due to its high charge mobility and potential applications in electronic, optical and optoelectronic devices. We demonstrate by molecular dynamics and nonadiabatic quantum dynamics simulations that the excitation of out-of-plane acoustic phonon (ZA) provides strong modulation of the band gap, carrier lifetime and carrier mobility in BP. A 1% tensile strain can significantly enhance ZA mode excitation at room temperature, distinctly reducing the band gap, carrier mobility, and lifetime. These electronic properties can be tuned easily by influencing the excitation amplitude of the ZA mode. Unique to the family of two-dimensional materials, the ZA mode plays an essential role in controlling the electronic properties of BP. The results of our study provide valuable guidelines for design of functional nanodevices based on 2D BP.
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http://dx.doi.org/10.1021/acs.jpclett.1c00747DOI Listing
April 2021

Prediction of Freezing of Gait in Parkinson's Disease Using a Random Forest Model Based on an Orthogonal Experimental Design: A Pilot Study.

Front Hum Neurosci 2021 22;15:636414. Epub 2021 Mar 22.

Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

Purpose: The purpose of this study was to introduce an orthogonal experimental design (OED) to improve the efficiency of building and optimizing models for freezing of gait (FOG) prediction.

Methods: A random forest (RF) model was developed to predict FOG by using acceleration signals and angular velocity signals to recognize possible precursor signs of FOG (preFOG). An OED was introduced to optimize the feature extraction parameters.

Results: The main effects and interaction among the feature extraction hyperparameters were analyzed. The false-positive rate, hit rate, and mean prediction time (MPT) were 27%, 68%, and 2.99 s, respectively.

Conclusion: The OED was an effective method for analyzing the main effects and interactions among the feature extraction parameters. It was also beneficial for optimizing the feature extraction parameters of the FOG prediction model.
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http://dx.doi.org/10.3389/fnhum.2021.636414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044955PMC
March 2021

Low-Dose Corticosteroid Combined With Mycophenolate Mofetil for IgA Nephropathy With Stage 3 or 4 CKD: A Retrospective Cohort Study.

Clin Ther 2021 Apr 13. Epub 2021 Apr 13.

Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address:

Purpose: This study assessed the long-term (10-year) tolerability and efficacy of a low-dose corticosteroid combined with mycophenolate mofetil (CS + MMF) in the treatment of immunoglobulin A nephropathy (IgAN) with stage 3/4 chronic kidney disease and proteinuria in clinical practice in China.

Methods: Data from patients with biopsy-proven IgAN, stage 3/4 chronic kidney disease (estimated glomerular filtration rate 15-59 mL/min/1.73 m), and proteinuria (urinary protein excretion ≥1.0 g/d) and who were treated with uncontrolled supportive care (USC), CS, or CS + MMF between January 2008 and December 2017 were included. The primary end point was the prevalence of the composite outcome of any of the following conditions: a reduction in estimated glomerular filtration rate of ≥50%, end-stage renal disease, and death.

Findings: Of the 120 enrolled patients, 44, 25, and 51 were treated with USC, CS, and CS + MMF, respectively. The median follow-up time was 40.1 months (IQR, 29.1-67.8 months). The prevalences of the composite outcome were 63.6%, 56.0%, and 19.6%, respectively (P < 0.001). The cumulative 5-year renal function-preservation rates were 48.1%, 51.4%, and 83.7%. After adjustment for covariates, the prevalence of the composite outcome was significantly decreased with CS + MMF (HR = 0.094; 95% CI, 0.026-0.335; P < 0.001), but not with CS (HR = 0.749; 95% CI, 0.354-1.583; P = 0.449), compared with USC. However, 4 patients in the CS + MMF group died, of whom 3 had severe pneumonia.

Implications: CS + MMF may have more promising efficacy than USC or CS in renal-function preservation in patients with IgAN and chronic kidney disease in the Chinese population. However, attention should be paid to the increased risk for death due to severe pneumonia.
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http://dx.doi.org/10.1016/j.clinthera.2021.03.009DOI Listing
April 2021

Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro.

Biomed Res Int 2021 29;2021:5582648. Epub 2021 Mar 29.

Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, Guangdong 516029, China.

Lung cancer remains the leading cause of cancer death worldwide. Late diagnosis, chemoresistance, and metastasis are the main reasons for the high mortality rate of lung cancer. Therefore, the development of other treatments is urgent. Cediranib (CED), a vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, shows promising antitumour activities in various cancers including lung cancer. Here, we explored the effects and the underlying molecular mechanism of CED on non-small-cell lung cancer (NSCLC) cell line A549 cells in vitro. Our results show that CED could inhibit A549 cell proliferation and cloning formation. Meanwhile, G1 phase cell cycle arrest was also found, as featured by the increased proportion of G1 phase cells as well as the reduction of G1 phase relative proteins CDK4/cyclin D1 and CDK2/cyclin E. Moreover, the ratio of LC3-II/LC3-I was elevated significantly in CED-treated groups compared with the controls. Furthermore, the expression of p-Akt, p-P38, p-Erk1/2, and p-mTOR proteins was decreased obviously in the treatment groups. These results suggest that CED could induce apoptosis and G1 phase cell cycle arrest in A549 cells. Meanwhile, CED may induce autophagy through MAPK/Erk1/2 and Akt/mTOR signal pathway in A549 cells.
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http://dx.doi.org/10.1155/2021/5582648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024085PMC
March 2021

Effects of Vision Health Education and Free Eyeglasses on Knowledge of Vision and Usage of Spectacles Among Primary School Students: Evidence from Gansu and Shaanxi Provinces in China.

Risk Manag Healthc Policy 2021 9;14:1449-1464. Epub 2021 Apr 9.

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Background: In rural China, children's vision problems are very common, with many who would benefit from refractive correction not getting the care they need. This study examines whether a health information campaign that involves vision health education and a free trial of health product with free eyeglasses is effective at raising students' awareness of myopia and promoting students' eyeglasses usage.

Methods: We conducted an in-the-field randomized controlled experiment of a program providing vision health education and subsidized free eyeglasses to myopic children from 168 primary schools in rural Northwestern China in 2012.

Results: A total of 2189 students, mean age 10.5 years (49.3% male), participated in the baseline survey. At the baseline, the average correct response rate for visual knowledge among the sample students was 30.1%, and only 15% who needed eyeglasses used them. Seven months after intervention, the average correct response rate for vision knowledge were 48.5% and 48.3% in the education group and the education plus free eyeglasses group respectively, significantly higher than that of the control group. The rate of eyeglasses usage was 36% and 43% in the free eyeglasses group and the education plus free eyeglasses group respectively, significantly higher than that of the control group. The rate of eyeglasses compliance in the free eyeglasses group and the education plus free eyeglasses group was 19% and 26%, which also were significantly higher than the control group.

Conclusion: The information campaign combined with subsidized eyeglasses had a better effect both on vision knowledge and eyeglasses usage. The information campaign improved knowledge by providing the right information, and free eyeglasses changed the perceived utility and experience by the students using the product and getting benefits. Information and the free eyeglasses (subsidized) are complements.
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http://dx.doi.org/10.2147/RMHP.S297265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044073PMC
April 2021

MicroRNA-26b-5p Targets DAPK1 to Reduce Intestinal Ischemia/Reperfusion Injury via Inhibition of Intestinal Mucosal Cell Apoptosis.

Dig Dis Sci 2021 Apr 10. Epub 2021 Apr 10.

Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Background: Emerging evidence has suggested that miRNAs are important regulators of intestinal I/R injury, but their function in this context remains elusive.

Aims: To evaluate the role of miR-26b-5p in intestinal I/R injury.

Methods: We utilized in vivo murine models of intestinal I/R and in vitro Mode-K cell-based models of oxygen and glucose deprivation/reperfusion (OGD/R) to examine the function of miR-26b-5p in intestinal I/R injury. The expression of miR-26b-5p in intestinal mucosa and Mode-K cell was detected by RT-PCR. HE staining and Chiu's score were used to evaluate intestinal mucosa injury severity. Apoptosis was detected by TUNEL stain, flow cytometry, and western blot. TargetScan and StarBase prediction algorithms were applied to predict putative target genes of miR-26b-5p and validated by luciferase reporter analyses.

Results: We found that the expression of miR-26b-5p in intestinal mucosa was markedly decreased during I/R injury. We additionally found miR-26b-5p overexpression to markedly disrupt intestinal I/R- or OGD/R-induced injury in vivo and in vitro, whereas inhibiting this miRNA had an adverse impact and resulted in increased intestinal tissue injury and Mode-K cell damage. From a mechanistic perspective, miR-26b-5p was predicted to target DAPK1, which was related to cellular apoptosis. Luciferase reporter assay results confirmed that miR-26b-5p directly targets DAPK1 in Mode-K cells, thereby suppressing OGD/R-induced cell apoptosis.

Conclusion: Our findings show that miR-26b-5p may prevent intestinal I/R injury via targeting DAPK1 and inhibiting intestinal mucosal cell apoptosis, suggesting that this miRNA may be a viable target for the treatment of intestinal I/R injury.
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http://dx.doi.org/10.1007/s10620-021-06975-7DOI Listing
April 2021

A vicious cycle of bisretinoid formation and oxidation relevant to recessive Stargardt disease.

J Biol Chem 2021 Jan 7;296:100259. Epub 2021 Jan 7.

Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address:

The ability of iron to transfer electrons enables the contribution of this metal to a variety of cellular activities even as the redox properties of iron are also responsible for the generation of hydroxyl radicals (OH), the most destructive of the reactive oxygen species. We previously showed that iron can promote the oxidation of bisretinoid by generating highly reactive hydroxyl radical (OH). Now we report that preservation of iron regulation in the retina is not sufficient to prevent iron-induced bisretinoid oxidative degradation when blood iron levels are elevated in liver-specific hepcidin knockout mice. We obtained evidence for the perpetuation of Fenton reactions in the presence of the bisretinoid A2E and visible light. On the other hand, iron chelation by deferiprone was not associated with changes in postbleaching recovery of 11-cis-retinal or dark-adapted ERG b-wave amplitudes indicating that the activity of Rpe65, a rate-determining visual cycle protein that carries an iron-binding domain, is not affected. Notably, iron levels were elevated in the neural retina and retinal pigment epithelial (RPE) cells of Abca4 mice. Consistent with higher iron content, ferritin-L immunostaining was elevated in RPE of a patient diagnosed with ABCA4-associated disease and in RPE and photoreceptor cells of Abca4 mice. In neural retina of the mutant mice, reduced Tfrc mRNA was also an indicator of retinal iron overload. Thus iron chelation may defend retina when bisretinoid toxicity is implicated in disease processes.
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http://dx.doi.org/10.1016/j.jbc.2021.100259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948646PMC
January 2021

Weaning Age Affects the Development of the Ruminal Bacterial and Archaeal Community in Hu Lambs During Early Life.

Front Microbiol 2021 23;12:636865. Epub 2021 Mar 23.

Department of Animal Sciences, The Ohio State University, Columbus, OH, United States.

Weaning plays an important role in many animal processes, including the development of the rumen microbiota in ruminants. Attaining a better understanding of the development of the rumen microbial community at different weaning stages can aid the identification of the optimal weaning age. We investigated the effects of weaning age on ruminal bacterial and archaeal communities in Hu lambs. Thirty male Hu lambs were randomly assigned to two weaning-age groups: a group weaned at 30 days of age (W30) and a group weaned at 45 days of age (W45), with each group having five replicate pens. On the weaning day (day 30 for W30 and day 45 for W45) and at 5 days postweaning [day 35 for W30 (PW30) and day 50 for W45 (PW45)], one lamb from each replicate was randomly selected and sacrificed. Rumen contents were collected to examine the ruminal microbiota. Compared to W30, PW30 had a decreased relative abundance of . At genus level, the extended milk replacer feeding (W45 vs. W30) increased the relative abundance of while decreased that of and . Compared to W30, PW30 exhibited decreased relative abundances of , and but an increased unclassified . No significant difference was noted in the detected archaeal taxa among the animals. The function "biosynthesis of secondary metabolites" was less predominant in PW30 than in W30, whereas the opposite held true for "metabolism of cofactors and vitamins." Some bacterial genera were significantly correlated with rumen volatile fatty acid (VFA) concentration or other animal measures, including negative correlations between ruminal VFA concentration and unclassified and unclassified ; positive correlations of ruminal papillae length with and , but negative correlations with and ; and negative correlations between plasma D-lactate concentration and , unclassified , and . Our results revealed that the ruminal bacterial community underwent larger changes over time in lambs weaned at 30 days of age than in lambs weaned half a month later. Thus, extending milk replacer feeding to 45 days weaning was recommended from the perspective of the rumen microbial community in the Hu lamb industry.
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http://dx.doi.org/10.3389/fmicb.2021.636865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021712PMC
March 2021

Dissipative preparation of qutrit entanglement via periodically modulated Rydberg double antiblockade.

Opt Express 2021 Mar;29(7):10117-10133

We propose a mechanism of Rydberg double antiblockade by virtue of a resonant dipole-dipole interaction between a pair of Rydberg atoms placed at short distances scaling as 1/R. By combining this novel excitation regime with microwave-driven fields and dissipative dynamics, a stationary qutrit entangled state can be obtained with high quality, the corresponding steady-state fidelity and purity are insensitive to the variations of the dynamical parameters. Furthermore, we introduce time-dependent laser fields with periodically modulated amplitude to speed up the entanglement creation process. Numerical simulations reveal that the order of magnitude of the shortened convergence time is about 10 in units of ω, and the acceleration effect appears valid in broad parametric space. The present results enrich the physics of the Rydberg antiblockade regimes and may receive more attention for the experimental investigations in dissipative dynamics of neutral atoms.
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http://dx.doi.org/10.1364/OE.419568DOI Listing
March 2021

Dissipative preparation of qutrit entanglement via periodically modulated Rydberg double antiblockade.

Opt Express 2021 Mar;29(7):10117-10133

We propose a mechanism of Rydberg double antiblockade by virtue of a resonant dipole-dipole interaction between a pair of Rydberg atoms placed at short distances scaling as 1/R. By combining this novel excitation regime with microwave-driven fields and dissipative dynamics, a stationary qutrit entangled state can be obtained with high quality, the corresponding steady-state fidelity and purity are insensitive to the variations of the dynamical parameters. Furthermore, we introduce time-dependent laser fields with periodically modulated amplitude to speed up the entanglement creation process. Numerical simulations reveal that the order of magnitude of the shortened convergence time is about 10 in units of ω, and the acceleration effect appears valid in broad parametric space. The present results enrich the physics of the Rydberg antiblockade regimes and may receive more attention for the experimental investigations in dissipative dynamics of neutral atoms.
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http://dx.doi.org/10.1364/OE.419568DOI Listing
March 2021

IT-SVO: Improved Semi-Direct Monocular Visual Odometry Combined with JS Divergence in Restricted Mobile Devices.

Sensors (Basel) 2021 Mar 12;21(6). Epub 2021 Mar 12.

School of Mechanical Engineering, Guizhou University, Guiyang 550025, China.

Simultaneous localization and mapping (SLAM) has a wide range for applications in mobile robotics. Lightweight and inexpensive vision sensors have been widely used for localization in GPS-denied or weak GPS environments. Mobile robots not only estimate their pose, but also correct their position according to the environment, so a proper mathematical model is required to obtain the state of robots in their circumstances. Usually, filter-based SLAM/VO regards the model as a Gaussian distribution in the mapping thread, which deals with the complicated relationship between mean and covariance. The covariance in SLAM or VO represents the uncertainty of map points. Therefore, the methods, such as probability theory and information theory play a significant role in estimating the uncertainty. In this paper, we combine information theory with classical visual odometry (SVO) and take Jensen-Shannon divergence (JS divergence) instead of Kullback-Leibler divergence ( divergence) to estimate the uncertainty of depth. A more suitable methodology for SVO is that explores to improve the accuracy and robustness of mobile devices in unknown environments. Meanwhile, this paper aims to efficiently utilize small portability for location and provide a priori knowledge of the latter application scenario. Therefore, combined with SVO, JS divergence is implemented, which has been realized. It not only has the property of accurate distinction of outliers, but also converges the inliers quickly. Simultaneously, the results show, under the same computational simulation, that SVO combined with JS divergence can more accurately locate its state in the environment than the combination with divergence.
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http://dx.doi.org/10.3390/s21062025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998773PMC
March 2021

Preparation of cellulose nanospheres via combining ZnCl·3HO pretreatment and p-toluenesulfonic hydrolysis as a two-step method.

Int J Biol Macromol 2021 Mar 30;181:621-630. Epub 2021 Mar 30.

Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, PR China; School of Material Science and Engineering, Tianjin University, Tianjin 300072, PR China.

Spherical nanocelluloses, also known as cellulose nanospheres (CNS), have controllable morphology and have shown advantages as green template material, emulsion stabilizer. Herein, CNS were prepared via a new two-step method, first pretreatment of microcrystalline cellulose (MCC) using ZnCl·3HO and then acid hydrolysis of regenerated cellulose (RC) via p-toluenesulfonic acid (p-TsOH). The shape, size, crystallinity of MCC were changed, and nubbly RC with smallest size (942 nm) was obtained after 2 h pretreatment by ZnCl·3HO. CNS with high 61.3% yield were produced after acid hydrolysis (67 wt% p-TsOH) of RC at 80 °C, 6 h. The analysis of Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) showed that CNS had an average diameter of 347 nm. CNS were present in precipitate after high-speed centrifugation, due to the high Zeta potential of -12 mV and large size. The structure of CNS was tested by Fourier Transfer Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Nuclear Magnetic Resonance (NMR), CNS had high crystallinity (cellulose II) of 61%. Thermal Gravimetric Analysis (TGA) indicated that CNS had high thermal stability (T 303.3 °C, T 332 °C). CNS showed poor re-dispersibility in water/ethanol/THF, 1 wt% CNS could be dissolved in ZnCl·3HO. 7.37% rod-like CNC were obtained after 6 h hydrolysis. FTIR proved that p-TsOH was recovered by re-crystallization. This study provided a novel, sustainable two-step method for the preparation of spherical CNS.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.168DOI Listing
March 2021

Liu Shen Wan inhibits influenza virus-induced secondary Staphylococcus aureus infection in vivo and in vitro.

J Ethnopharmacol 2021 Mar 22:114066. Epub 2021 Mar 22.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China; Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou, China. Electronic address:

Ethnopharmacological Relevance: Liu Shen Wan (LSW) is a traditional Chinese medicine (TCM) with detoxification and antiphlogistic activity; it is composed of bezoar, toad venom, musk, pearl powder, borneol and realgar. In recent years, LSW has been widely used in traditional medicine for the treatment of influenza, tonsillitis, pharyngitis, mumps, cancer and leukaemia.

Aim Of Study: The anti-influenza virus properties of LSW and its inhibition of the inflammatory response was demonstrated in our previous research; however, the effect and potential mechanism of LSW against influenza induced secondary bacteria have remained obscure. Therefore, in the present study, a model of influenza virus PR8 with secondary infection by Staphylococcus aureus (S. aureus) in vitro and in mice was established to examine the effect and potential mechanism by which LSW inhibits bacterial adhesion and subsequent severe pneumonia after viral infection.

Materials And Methods: We investigated the effect of LSW on the PR8-induced adhesion of live S. aureus in A549 cells. qRT-PCR was used to detect the expression of adhesion molecules. Western blotting was used to determine the expression of CEACAM1, RIG-1, MDA5, p-NF-κB, and NF-κB in A549 cells. Inflammatory cytokines were detected using a Bio-Plex Pro Human Cytokine Screening Panel (R&D) in A549 cells and Mouse Magnetic Luminex Assays (R&D) in mice infected with PR8 virus and secondarily with S. aureus, respectively. Moreover, the survival rate, lung index, viral titre, bacterial loads and pathological changes in the lung tissue of mice infected with PR8 and S. aureus were investigated to estimate the effect of LSW in inhibiting severe pneumonia.

Results: LSW significantly decreased S. aureus adhesion following influenza virus infection in A549 cells, which may have occurred by suppressing expression of the adhesion molecule CEACAM1. In addition, treatment with LSW dramatically suppressed the induction of proinflammatory cytokines (CCL2/MCP-1 and CXCL-9/MIG) and chemokines (IL-6 and TNF-α) by PR8 infection following secondary LPS stimulation in A549 cells. Upregulation of related signalling proteins (RIG-I, MDA5 and NF-κB) induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly decreased the viral titres and bacterial load, prolonged survival time, and ameliorated lung inflammation and injury in mice with S. aureus infection secondary to PR8 infection.

Conclusions: We demonstrated that LSW prevents S. aureus adherence to influenza virus-infected A549 cells, perhaps by inhibiting the expression of the adhesion molecule CEACAM1. The upregulation of proinflammatory cytokines and related signalling proteins induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly ameliorated lung injury caused by viral and secondary bacterial infection. These findings provide a further evaluation of LSW and suggest a beneficial effect of LSW for the prevention of secondary bacterial infection and related complications.
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http://dx.doi.org/10.1016/j.jep.2021.114066DOI Listing
March 2021

Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage.

J Neuroinflammation 2021 Mar 23;18(1):81. Epub 2021 Mar 23.

Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou, Gansu, 730000, People's Republic of China.

Background: Ischemia can induce rapid activation of microglia in the brain. As key immunocompetent cells, reactive microglia play an important role in pathological development of ischemic stroke. However, the role of activated microglia during the development of ischemia remains controversial. Thus, we aimed to investigate the function of reactive microglia in the early stage of ischemic stroke.

Methods: A Rose Bengal photothrombosis model was applied to induce targeted ischemic stroke in mice. CX3CR1:R26 mice were used to specifically deplete resident microglia through intragastric administration of tamoxifen (Ta) and intraperitoneal injection of diphtheria toxin (DT). At day 3 after ischemic stroke, behavioral tests were performed. After that, mouse brains were collected for further histological analysis and detection of mRNA expression of inflammatory factors.

Results: The results showed that specific depletion of microglia resulted in a significant decrease in ischemic infarct volume and improved performance in motor ability 3 days after stroke. Microglial depletion caused a remarkable reduction in the densities of degenerating neurons and inducible nitric oxide synthase positive (iNOS) cells. Importantly, depleting microglia induced a significant increase in the mRNA expression level of anti-inflammatory factors TGF-β1, Arg1, IL-10, IL-4, and Ym1 as well as a significant decline of pro-inflammatory factors TNF-α, iNOS, and IL-1β 3 days after stroke.

Conclusions: These results suggest that activated microglia is an important modulator of the brain's inflammatory response in stroke, contributing to neurological deficit and infarct expansion. Modulation of the inflammatory response through the elimination of microglia at a precise time point may be a promising therapeutic approach for the treatment of cerebral ischemia.
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http://dx.doi.org/10.1186/s12974-021-02127-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986495PMC
March 2021

Complex anthropogenic interaction on vegetation greening in the Chinese Loess Plateau.

Sci Total Environ 2021 Feb 25;778:146065. Epub 2021 Feb 25.

The Chongqing Engineering Research Center for Spatial Big Data Intelligent Technology, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

Vegetation greening steered by land use management in the Chinese Loess Plateau has been widely reported, however studies that quantitatively assessing and explicitly linking the anthropogenic forcing on vegetation greening and browning are scarce. Here in this study, we calculate the increment and rate of change of fractional vegetation cover (FVC) from 1998 to 2018 in the Loess Plateau, and compare the results with changing rainfall, soil types, and Gross Domestic Product (GDP), to detail a systematic assessment of the role of the climate-vegetation-human nexus. We have observed that nearly 80% of the study area has undergone greening, and noticed that rainfall was not the main driver of rapid vegetation change, instead of human land use management such as, irrigation along the Yellow River, snowmelt-runoff irrigation, and irrigation from reservoirs formed by check dams contributed the most for the increased FVC in the Chinese Loess Plateau. Concurrently, rapid vegetation browning is almost fully driven by urban expansion. Our findings show that GDP growth promotes both browning and greening, indicative of sustainable development in the Loess plateau region. These contrasting trends reveal that the relationship between human activities and greening is very complex.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146065DOI Listing
February 2021