Publications by authors named "Zhang Chen"

2,282 Publications

  • Page 1 of 1

Environmental chemical exposures in the urine of dogs and people sharing the same households.

J Clin Transl Sci 2020 Oct 2;5(1):e54. Epub 2020 Oct 2.

Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.

Introduction: Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity. We hypothesize that dogs with UCC may act as sentinels for human urothelial carcinogen exposures. The aim of this pilot study was to determine whether healthy people and dogs in the same households share urinary exposures to potentially mutagenic chemical carcinogens.

Methods: We measured urinary concentrations of acrolein (as its metabolite 3-HPMA), arsenic species, 4-aminobiphenyl, and 4-chlorophenol (a metabolite of the phenoxyherbicide 2,4-D) in healthy dogs and their owners. We assessed possible chemical sources through questionnaires and screened for urothelial DNA damage using the micronucleus assay.

Results: Biomarkers of urinary exposure to acrolein, arsenic, and 4-chlorophenol were found in the urine of 42 pet dogs and 42 owners, with 4-aminobiphenyl detected sporadically. Creatinine-adjusted urinary chemical concentrations were significantly higher, by 2.8- to 6.2-fold, in dogs compared to humans. Correlations were found for 3-HPMA ( = 0.32, = 0.04) and monomethylarsonic acid ( = 0.37, = 0.02) between people and their dogs. Voided urothelial cell yields were inadequate to quantify DNA damage, and questionnaires did not reveal significant associations with urinary chemical concentrations.

Conclusions: Healthy humans and pet dogs have shared urinary exposures to known mutagenic chemicals, with significantly higher levels in dogs. Higher urinary exposures to acrolein and arsenic in dogs correlate to higher exposures in their owners. Follow-up studies will assess the mutagenic potential of these levels and measure these biomarkers in owners of dogs with UCC.
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http://dx.doi.org/10.1017/cts.2020.548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057441PMC
October 2020

Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids.

Chirality 2021 May 3. Epub 2021 May 3.

College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, China.

(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.
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http://dx.doi.org/10.1002/chir.23312DOI Listing
May 2021

Ordered inverse-opal scaffold based on bionic transpiration to create a biomimetic spine.

Nanoscale 2021 Apr 30. Epub 2021 Apr 30.

State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.

The availability of functional spinal cord scaffolds for nerve tissue engineering (NTE) strategies is an urgent clinical demand for spinal transplantation. However, effective transplanted spinal cord scaffolds are restricted by poor mechanical integrity, topological cues, complex processing, or other properties. Hence, this work aims to fabricate a new three-dimensional (3D) scaffold with electrically micropatterned materials for structural spinal mimicry. Inspired by plant transpiration, the scaffold templates are formed by self-assembled colloidal crystals in a glass capillary after the solvent evaporates gradually. Replicated from bionic transpiration photonic crystal templates, the specific 3D conductive inter-surface ordered microstructures are fabricated through carbonization and corrosion. Nerve cell reconstruction on columnar scaffolds indicated that these conductive porous materials were of excellent biocompatibility. Meanwhile, due to the homogeneously interconnected architecture characteristics, the inverse opal structures facilitated the connection and information transmission between nerve cells. Statistics on the number and length of neural neurites indicated that the microstructures with uniform pores guided nerve cell neurite growth and development. These biomimetic spine properties make them potential alternative scaffolds for nerve tissue engineering.
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http://dx.doi.org/10.1039/d1nr00731aDOI Listing
April 2021

Imaging of Non-ossifying Fibromas: A Case Series.

Cureus 2021 Mar 25;13(3):e14102. Epub 2021 Mar 25.

Trauma and Orthopaedics, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, GBR.

Non-ossifying fibromas (NOFs) are common lesions most frequently found in the growing bones of children and adolescents. Although NOFs are benign, their presence as incidental findings often triggers further investigation as they are sometimes mistaken for more sinister bone lesions such as aneurysmal bone cysts. NOFs can also pose an increased risk of pathological fractures. However, there are currently no guidelines on the follow-up of NOFs. We present a case series of five patients from Addenbrooke's Hospital with NOFs illustrating their morphological features on plain radiographs and highlighting specific characteristics to support clinicians in diagnosing and managing NOFs.
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http://dx.doi.org/10.7759/cureus.14102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075760PMC
March 2021

Information-Efficient, Off-Center Sampling Results in Improved Precision in 3D Single-Particle Tracking Microscopy.

Entropy (Basel) 2021 Apr 22;23(5). Epub 2021 Apr 22.

Department of Chemistry, Duke University, Durham, NC 27708, USA.

In this work, we present a 3D single-particle tracking system that can apply tailored sampling patterns to selectively extract photons that yield the most information for particle localization. We demonstrate that off-center sampling at locations predicted by Fisher information utilizes photons most efficiently. When performing localization in a single dimension, optimized off-center sampling patterns gave doubled precision compared to uniform sampling. A ~20% increase in precision compared to uniform sampling can be achieved when a similar off-center pattern is used in 3D localization. Here, we systematically investigated the photon efficiency of different emission patterns in a diffraction-limited system and achieved higher precision than uniform sampling. The ability to maximize information from the limited number of photons demonstrated here is critical for particle tracking applications in biological samples, where photons may be limited.
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http://dx.doi.org/10.3390/e23050498DOI Listing
April 2021

Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo.

Molecules 2021 Apr 11;26(8). Epub 2021 Apr 11.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.
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http://dx.doi.org/10.3390/molecules26082199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070450PMC
April 2021

A Preliminary Investigation on Plasma Cell Adhesion Molecules Levels by Protein Microarray Technology in Major Depressive Disorder.

Front Psychiatry 2021 12;12:627469. Epub 2021 Apr 12.

Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Major depressive disorder (MDD) is a serious mental disorder, and there is a great difficulty to diagnose and treat. Hitherto, relatively few studies have explored the correlation between the levels of plasma cell adhesion molecules and MDD. Thirty outpatients with acute episodes of MDD in Shanghai Mental Health Center and 34 healthy volunteers from the community were recruited as subjects. Protein microarray technology was applied to compared the differences in plasma levels of 17 kinds of adhesion molecular proteins between the two groups. Meanwhile, the diagnostic value of different proteins in depression was discussed by using the receiver operating characteristic curve. The levels of Carcinoembryonic Antigen Related Cell Adhesion Molecule-1(CEACAM-1) and Neural Cell Adhesion Molecule (NrCAM) in MDD patients were significantly higher than those in healthy controls ( < 0.05). The area under ROC curve of CEACAM-1 combined with NrCAM was 0.723, with the sensitivity 0.800 and the specificity 0.676. The plasma levels of CEACAM-1 and NrCAM were significantly up-regulated in MDD, and their combined application was of potential diagnostic value, deserving to expand the sample size for further verification.
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http://dx.doi.org/10.3389/fpsyt.2021.627469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071998PMC
April 2021

Activities of PMO optical space debris survey.

An Acad Bras Cienc 2021 23;93(suppl 1):e20200827. Epub 2021 Apr 23.

Purple Mountain Observatory (PMO), No. 10 Yuanhua Road, Qixia District, 210023, Nanjing, China.

Space debris division of PMO is devoted to play an important role in the research of orbital mechanics and the development of space debris observation techniques in China. To support the work, this division builds and operates a large optical network across China. The observational network include two major subsets, large field survey telescopes and precise tracking telescopes. The main objective of the network is to maintain cataloged orbital debris and detect uncatalogued debris. CHES at YaoAn site is the most recent facility, for higher orbits survey. New operational software and data pipeline that aims at detecting unresolved objects has being developed. This paper presents the details of this facility and related activities.
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http://dx.doi.org/10.1590/0001-3765202120200827DOI Listing
April 2021

Neural biomarker of functional disability in major depressive disorder: A structural neuroimaging study.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Apr 24:110337. Epub 2021 Apr 24.

Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China; Shanghai Key Laboratory of Psychotic disorders, Shanghai 201108, China. Electronic address:

Background: Most patients with the major depressive disorder (MDD) have varying degrees of impaired social functioning, and functional improvement often lags behind symptomatic improvement. However, it is still unclear if certain neurobiological factors underlie the deficits of social function in MDD. The aim of this study was to investigate the biomarkers of social function in MDD using structural magnetic resonance imaging (MRI).

Methods: 3T anatomical MRI was obtained from 272 subjects including 46 high-functioning (high-SF, Sheehan Disability Scale (SDS) rating < 18) and 63 low-functioning (low-SF, SDS score ≥ 18) patients with MDD and 163 healthy controls (HC). Voxel-based morphometry (VBM) was employed to locate brain regions with grey matter (GM) volume differences in relation to social function in MDD. Regions showing GM differences in relation to social function at baseline were followed up longitudinally in a subset of 38 patients scanned after 12-week treatment.

Results: Volume of right parahippocampal gyrus (rPHG) was significantly reduced in low-SF patients with MDD when compared to high-SF ones (FDR-corrected p < 0.05). Over 12 weeks of follow-up, though SF improved overall, the high and low-SF subgroups continued to differ in their SF, but had no progressive changes in PHG volume.

Limitations: Limited functional assessment, high drop-out rate and median-based grouping method.

Conclusions: Greater GM volume (GMV) of the rPHG may mark better social function in patients with MDD.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110337DOI Listing
April 2021

Ecological and Syndemic Predictors of Drug Use During Sex and Transactional Sex among U.S. Black Men Who Have Sex with Men: A Secondary Data Analysis from the HPTN 061 Study.

Arch Sex Behav 2021 Apr 26. Epub 2021 Apr 26.

Yale University School of Nursing, New Haven, CT, USA.

Threats to sexual health among U.S. Black men who have sex with men (MSM) may manifest in a context of social adverse experiences. Situational sex is one such context, which we characterize as sexual behaviors driven either by a desire to cultivate a specific sexual experience or attributable to social vulnerability. Two characterizations of situational sex explored in this study were drug use during sex and transactional sex. Guided by ecological and syndemic frameworks, we conducted a secondary data analysis of social conditions and sexual behaviors among a prospective cohort of Black MSM from the HIV Prevention Trial Network (HPTN) 061 study. Using structural equation modeling, this analysis examined the indirect effect of syndemic factors (substance use, depression, violence exposure) in the relationship between ecological constructs (anti-Black/homophobic stigma, childhood violence, and economic vulnerability) and situational sex (drug use during sex, transactional sex). Model fit indices, CFI (.870) and SRMR (.091), demonstrated reasonable fit. Significant indirect effects emerged via substance use for economic vulnerability (indirect effect = .181, 95% CI [.078, .294]) and anti-Black/homophobic violence and stigma (indirect effect = .061, 95% CI [.008, .121]) on drug use during sex; as well as on transactional sex (economic vulnerability indirect effect = .059, 95% CI [.018, .121] and anti-Black/homophobic stigma and violence indirect effect = .020, 95% CI [.003, .051]). Findings implicate the need for social and fiscal intervention to address upstream, ecological, and syndemic factors that influence inherent vulnerability of situational sex and overall threats to sexual health among Black MSM.
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http://dx.doi.org/10.1007/s10508-020-01871-zDOI Listing
April 2021

A Stable NanoPAA-ZnO/ZnCl Composite with Variable 3D Structured Morphology and Sustained Superhydrophilicity.

Langmuir 2021 Apr 26. Epub 2021 Apr 26.

Joule Physics Laboratory, School of Science, Engineering and Environment, University of Salford, Salford, Greater Manchester M5 4WT, U.K.

A ZnO/ZnCl composite with stable 3D structural morphologies and long lasting superhydrophilicity was synthesized on the top surface of a nano porous anodic alumina (nanoPAA) substrate. The wettability of a nanoPAA-ZnO/ZnCl was systematically characterized and the experimental data indicated that the water contact angle (WCA) of 0° could be achieved as well as maintained over 7 days and still remained at 4.36° after 50 days, and its 3D structural morphology had no clearly observable change during this period. The mechanism for the superhydrophilicity of the composites was interpreted in terms of the inherent hydrophilicity of ZnO/ZnCl nanofilm, the three-dimensional structures of wrinkled nanoflakes, the nanogaps between neighbor nanoflakes, the difference of structual morphologies (i.e., size, shape, and upright posture of nanoflakes), and the measured True Volume of voids in the nanocomposite. The structural morphologies were mainly determined by the parameters such as the original concentration of precursor ZnCl and the pore diameter of nanoPAA substrate. The study proposes a promising superhydrophilic nanomaterial and a cost-effective synthesis method, which will play a practical role in the fields of biomedical molecular sensors and micro/nanofluidic chips.
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http://dx.doi.org/10.1021/acs.langmuir.0c03257DOI Listing
April 2021

Paper Information Recording and Security Protection Using Invisible Ink and Artificial Intelligence.

ACS Appl Mater Interfaces 2021 Apr 20;13(16):19443-19449. Epub 2021 Apr 20.

Key Laboratory of Micro-systems and Micro-structures Manufacturing of Ministry of Education, Institution Harbin Institute of Technology, Harbin 150001, China.

Conventional paper information protection mainly relies on stimuli-responsive functional materials that can display color or luminescence under external stimuli; however, this method is rather predictable and can be easily cracked. In this work, a paper information protection scheme combining fluorescent invisible ink and artificial intelligence was proposed. The ink was prepared by dissolving carbon nanoparticles in water, which has a high quantum yield and outstanding light stability and salt stability, thus ensuring the integrity of information in complex environments. A five-layer convolutional neural network (one of the two mainstream architectures in today's artificial intelligence fields) was specially trained based on ultraviolet light excited symbols printed by invisible ink. Using this scheme, the correct information could only be read with the specially trained neural network after ultraviolet (UV) irradiation. Without this trained neural network or UV irradiation, misleading messages will be presented. Moreover, it was possible to design unpredictable and highly complex password books to further increase information security. This smart strategy provides new opportunities for high-level paper information encryption and also proposes new ideas for the applications of carbon nanoparticles and artificial intelligence.
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http://dx.doi.org/10.1021/acsami.1c01179DOI Listing
April 2021

Hepatic differentiation of human embryonic stem cells by coupling substrate stiffness and microtopography.

Biomater Sci 2021 Apr 20. Epub 2021 Apr 20.

Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China.

Mechanical or physical cues are associated with the growth and differentiation of embryonic stem cells (ESCs). While the substrate stiffness or topography independently affects the differentiation of ESCs, their cooperative regulation on lineage-specific differentiation remains largely unknown. Here, four topographical configurations on stiff or soft polyacrylamide hydrogel were combined to direct hepatic differentiation of human H1 cells via a four-stage protocol, and the coupled impacts of stiffness and topography were quantified at distinct stages. Data indicated that the substrate stiffness is dominant in stemness maintenance on stiff gel and hepatic differentiation on soft gel while substrate topography assists the differentiation of hepatocyte-like cells in positive correlation with the circularity of H1 clones initially formed on the substrate. The differentiated cells exhibited liver-specific functions such as maintaining the capacities of CYP450 metabolism, glycogen synthesis, ICG engulfment, and repairing liver injury in CCl4-treated mice. These results implied that the coupling of substrate stiffness and topography, combined with the biochemical signals, is favorable to improve the efficiency and functionality of hepatic differentiation of human ESCs.
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http://dx.doi.org/10.1039/d1bm00174dDOI Listing
April 2021

Large-scale sequencing of flatfish genomes provides insights into the polyphyletic origin of their specialized body plan.

Nat Genet 2021 Apr 19. Epub 2021 Apr 19.

School of Ecology and Environment, Northwestern Polytechnical University, Xi'an, China.

The evolutionary and genetic origins of the specialized body plan of flatfish are largely unclear. We analyzed the genomes of 11 flatfish species representing 9 of the 14 Pleuronectiforme families and conclude that Pleuronectoidei and Psettodoidei do not form a monophyletic group, suggesting independent origins from different percoid ancestors. Genomic and transcriptomic data indicate that genes related to WNT and retinoic acid pathways, hampered musculature and reduced lipids might have functioned in the evolution of the specialized body plan of Pleuronectoidei. Evolution of Psettodoidei involved similar but not identical genes. Our work provides valuable resources and insights for understanding the genetic origins of the unusual body plan of flatfishes.
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http://dx.doi.org/10.1038/s41588-021-00836-9DOI Listing
April 2021

Ethanol Extracts of Regulate Ovarian Cancer Cell Proliferation, Apoptosis, and Epithelial-to-Mesenchymal Transition (EMT) via the ROS-Mediated p53 Pathway.

J Immunol Res 2021 1;2021:5569354. Epub 2021 Apr 1.

Department of Obstetrics and Gynecology, Zhuji Hospital Affiliated to Shaoxing University, Zhuji City 311800, China.

Ovarian cancer is a type of common gynecological tumors with high incidence and poor survival. The anticancer effects of the traditional Chinese medicine (SLT) have been intensively investigated in various cancers but in ovarian cancer is rare. The current study is aimed at investigating the effect of SLT on ovarian cancer cells. Lactate dehydrogenase (LDH) and MTT assays indicated that SLT concentrations of 0.25 and 0.5 g/mL were not cytotoxic and had significant inhibitory effects on the cell viabilities of A2780 and SKOV3 cells, hence were used for subsequent experiments. Flow cytometric and western blot analysis revealed that SLT effectively suppressed ovarian cancer cell proliferation via inducing cell cycle arrest and increasing apoptosis. Cell cycle and apoptosis-related protein expressions were also regulated in SLT-treated cells. Moreover, DCFH-DA and western blot assays demonstrated that SLT enhanced ROS accumulation and subsequently activated the p53 signaling pathway. However, SLT-regulated ovarian cancer cell proliferation, apoptosis, migration, invasion, and EMT were significantly reversed by an ROS inhibitor (NAC, N-acetyl-L-cysteine). Furthermore, A2780 and SKOV3 cells cocultured with M0 macrophages showed that SLT activated the polarization of M0 macrophages to M1 macrophages and inhibited the polarization to M2 macrophages, with the increased percentage of CD86+ cells and decreased percentage of CD206+ cells were detected. In summary, this study illustrated the anticancer effects of SLT on ovarian cancer cells, suggesting that SLT may have the potential to provide basic evidence for the discovery of antiovarian cancer agents.
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http://dx.doi.org/10.1155/2021/5569354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035038PMC
April 2021

The Association Between Notching of the Right Ventricular Outflow Tract Flow Velocity Doppler Envelope and Impaired Right Ventricular Function After Acute High-Altitude Exposure.

Front Physiol 2021 1;12:639761. Epub 2021 Apr 1.

Institute of Cardiovascular Diseases of PLA, The Second Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Introduction: Pulmonary artery pressure (PAP) is increased and right ventricular (RV) function is well preserved in healthy subjects upon exposure to high altitude (HA). An increase in PAP may trigger notching of the right ventricular outflow tract Doppler flow velocity envelope (RVOT notch), which is associated with impaired RV function in patients with pulmonary hypertension. However, whether HA exposure can induce RVOT notch formation and the subsequent impact on cardiac function in healthy subjects remains unclear.

Methods: A total of 99 subjects (69 males and 30 females) with a median age of 25 years were enrolled in this study; they traveled from 500 to 4100 m by bus over a 2-day period. All subjects underwent a comprehensive physiological and echocardiographic examination 1 day before ascension at low altitude and 15 ± 3 h after arrival at HA. The RVOT notch was determined by the presence of a notched shape in the RVOT Doppler flow velocity envelope. The systolic PAP (SPAP) was calculated as Bernoulli equation SPAP = 4 × (maximum tricuspid regurgitation velocity)+5 and mean PAP (mPAP) = 0.61 × SPAP+2. Cardiac output was calculated as stroke volume × heart rate. Pulmonary capillary wedge pressure (PCWP) was calculated as 1.9+1.24 × mitral E/e'. Pulmonary vascular resistance (PVR) was calculated as (mPAP-PCWP)/CO.

Results: After HA exposure, 20 (20.2%) subjects had an RVOT notch [notch (+)], and 79 (79.8%) subjects did not have an RVOT notch [notch (-)]. In the multivariate logistic regression analysis, the SPAP, right ventricular global longitude strain (RV GLS), and tricuspid E/A were independently associated with the RVOT notch. The SPAP, mPAP, PVR, standard deviations of the times to peak systolic strain in the four mid-basal RV segments (RVSD4), peak velocity of the isovolumic contraction period (ICV), and the peak systolic velocity (s') at the mitral/tricuspid annulus were increased in all subjects. Conversely, the pulse oxygen saturation (SpO), RV GLS, and tricuspid annulus plane systolic excursion (TAPSE)/SPAP were decreased. However, the increases of SPAP, mPAP, PVR, and RVSD4 and the decreases of SpO, RV GLS, and TAPSE/SPAP were more pronounced in the notch (+) group than in the notch (-) group. Additionally, increased tricuspid ICV and mitral/tricuspid s' were found only in the notch (-) group.

Conclusion: HA exposure-induced RVOT notch formation is associated with impaired RV function, including no increase in the tricuspid ICV or s', reduction of RV deformation, deterioration in RV-pulmonary artery coupling, and RV intraventricular synchrony.
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http://dx.doi.org/10.3389/fphys.2021.639761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047424PMC
April 2021

Calcium pectinate and hyaluronic acid modified lactoferrin nanoparticles loaded rhein with dual-targeting for ulcerative colitis treatment.

Carbohydr Polym 2021 Jul 27;263:117998. Epub 2021 Mar 27.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China. Electronic address:

Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in anti-UC.
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http://dx.doi.org/10.1016/j.carbpol.2021.117998DOI Listing
July 2021

L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4.

PLoS One 2021 15;16(4):e0250126. Epub 2021 Apr 15.

College of Animal Sciences, Zhejiang University, Hangzhou, China.

Amino acid metabolism plays an important role in controlling blood pressure by regulating the production of NO and ROS. The present study examined amino acid levels in the serum of Dahl SS rats and SS.13BN rats fed a low or high salt diet. We observed that 8 of 27 amino acids responded to a high salt diet in SS rats. Thus, we hypothesized that a defect in amino acids may contribute to the development of salt-induced hypertension. L-phenylalanine was used to treat SS rats with a low or high salt diet. The results demonstrated that L-phenylalanine supplementation significantly enhanced the serum nitrite levels and attenuated the high salt-induced hypertension in SS rats. Low levels of BH4 and nitrite and the impaired vascular response to acetylcholine were rescued by L-phenylalanine supplementation. Moreover, increased GTP cyclohydrolase (GCH1) mRNA, levels of BH4 and nitrite, and reduced superoxide production were observed in the kidneys of hypertensive SS rats with L-phenylalanine. The antihypertensive effects of L-phenylalanine might be mediated by enhancing BH4 biosynthesis and decreasing superoxide production from NO synthase, thereby protecting vascular and kidney function with reduced ROS and elevated NO levels. The present study demonstrated that L-phenylalanine supplementation restored vascular function, suggesting L-phenylalanine represented a potential target to attenuate high salt-sensitive hypertension through GCH1-BH4.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250126PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049246PMC
April 2021

Rough Carbon-Iron Oxide Nanohybrids for Near-Infrared-II Light-Responsive Synergistic Antibacterial Therapy.

ACS Nano 2021 04 15;15(4):7482-7490. Epub 2021 Apr 15.

Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.

Infections caused by multidrug resistant bacteria are still a serious threat to human health. It is of great significance to explore effective alternative antibacterial strategies. Herein, carbon-iron oxide nanohybrids with rough surfaces (RCF) are developed for NIR-II light-responsive synergistic antibacterial therapy. RCF with excellent photothermal property and peroxidase-like activity could realize synergistic photothermal therapy (PTT)/chemodynamic therapy (CDT) in the NIR-II biowindow with improved penetration depth and low power density. More importantly, RCF with rough surfaces shows increased bacterial adhesion, thereby benefiting both CDT and PTT through effective interaction between RCF and bacteria. antibacterial experiments demonstrate a broad-spectrum synergistic antibacterial effect of RCF against Gram-negative (), Gram-positive (), and methicillin-resistant (MRSA). In addition, satisfactory biocompatibility makes RCF a promising antibacterial agent. Notably, the synergistic antibacterial performances could be achieved employing the rat wound model with MRSA infection. The current study proposes a facile strategy to construct antibacterial agents for practical antibacterial applications by the rational design of both composition and morphology. RCF with low power density NIR-II light responsive synergistic activity holds great potential in the effective treatment of drug-resistant bacterial infections.
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http://dx.doi.org/10.1021/acsnano.1c00894DOI Listing
April 2021

miRNA-138-5p suppresses cigarette smoke-induced apoptosis in testicular cells by targeting Caspase-3 through the Bcl-2 signaling pathway.

J Biochem Mol Toxicol 2021 Apr 15:e22783. Epub 2021 Apr 15.

Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, PR China.

Long-term cigarette smoking (CS) can cause testicular toxicity, which interferes with normal spermatogenesis and leads to male infertility. One possible mechanism for this is the activation of the apoptosis signaling pathway, which leads to the irreversible apoptosis of testicular cells. However, the exact mechanism for this is not completely understood. Cell viability, cell apoptosis, and lactate dehydrogenase release assays were performed to elucidate the function of micro RNA (miRNA) in the pathogenesis of male testicular cell injury induced by CS. The results suggested that testicular cell injury was associated with CS both in vitro and in vivo. CS extract (CSE)-treated Leydig and Sertoli cells showed noticeable apoptosis. Based on the results of Agilent miRNA microarray and bioinformatics analyses, miRNA-138-5p was used in subsequent experiments. Quantitative polymerase chain reaction and Western blot assays showed a negative correlation between miR-138-5p and Caspase-3 expression. Transfection of miR-138-5p mimic significantly inhibited apoptosis and downregulated the expression of Caspase-3 in TM3 and TM4 cells. Furthermore, a dual-luciferase reporter assay demonstrated that miR-138-5p directly targeted Caspase-3 to regulate the apoptosis of testicular cells mediated by CSE. In addition, overexpression of miR-138-5p markedly downregulated the expression of p53 and Bak, which played critical roles in the Bcl-2 pathway. These results demonstrate that miRNA-138-5p inhibits CS-induced apoptosis in testicular cells by targeting Caspase-3 through the Bcl-2 signaling pathway.
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http://dx.doi.org/10.1002/jbt.22783DOI Listing
April 2021

Enhanced phenotype of calcipotriol-induced atopic dermatitis in filaggrin-deficient mice.

FASEB J 2021 May;35(5):e21574

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, P.R. China.

Impaired function of filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD). Several studies on FLG-deficient (Flg ) mice have indicated an essential role for FLG in the skin barrier and the development of AD, but none of the studies have described the characteristics on Flg mice with calcipotriol (CPT)-induced atopic dermatitis, which restricts the comprehensive understanding of functions of FLG. The present study sought to generate Flg mice and applied CPT to produce AD-like dermatitis for in vivo analysis of the FLG functions. CPT was applied on the skin of Flg mice to establish the AD-like dermatitis mouse model. The lesion inflammation was evaluated by gross ear thickness, histopathology, immunofluorescence, and cytokine production. Also, mucopolysaccharide polysulfate (MPS) and ceramide were used to observe the therapeutic function in this model. The results showed that the inflammation of CPT-induced dermatitis in Flg mice was more severer than that of wild-type (WT) mice, as evident by the increased level of gross appearance, ear thickness, inflammatory cell infiltration (mast cells and CD3 T cells), and inflammatory cytokine expression (interleukin (IL)-4, IL-6, IL-13, and thymic stromal lymphopoietin (TSLP)). The emollients MPS and ceramide partially restored the epidermal function and alleviated the skin inflammation in Flg mice with CPT-induced AD-like dermatitis. The current study demonstrated that skin barrier protein FLG is critical in the pathogenesis of AD. Also, the AD mouse model induced by CPT in Flg mice could be utilized to search for drug targets in AD.
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http://dx.doi.org/10.1096/fj.202002709RDOI Listing
May 2021

Pyrrolic Type N Directed Borylation Route to BN-PAHs: Tuning the Photophysical Properties by Varying the Conjugation Shape and Size.

J Org Chem 2021 Apr 14. Epub 2021 Apr 14.

Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China.

Two series of BN-cyclopenta[]phenalenes have been synthesized through an indole/pyrrole oriented borylation reaction. A total of five compounds are obtained and fully characterized; one of them is unambiguously confirmed by single X-ray crystal structure. Their photophysical properties could be finely tuned through varying the conjugation size and shape of the bottom PAHs applied. Moreover, their response toward fluoride anions was also investigated.
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http://dx.doi.org/10.1021/acs.joc.1c00142DOI Listing
April 2021

Influence of Rahnella aquatilis on arsenic accumulation by Vallisneria natans (Lour.) Hara for the phytoremediation of arsenic-contaminated water.

Environ Sci Pollut Res Int 2021 Apr 13. Epub 2021 Apr 13.

Hunan Province Key Laboratory of Coal Resources Clean-utilization and Mine Environment Protection, Hunan University of Science and Technology, Xiangtan, 411201, People's Republic of China.

Vallisneria natans (Lour.) Hara is a suitable submerged plant for the phytoremediation of As-contaminated water. Rahnella aquatilis is one of the plant growth-promoting rhizobacteria. Influences of R. aquatilis on the arsenic accumulation and detoxification of V. natans were investigated. The results showed that As accumulation by V. natans could be significantly improved after R. aquatilis inoculated at the lower level of As (< 2 mg/L). At 0.5, 1, and 2 mg/L As levels, the As concentrations of V. natans with R. aquatilis were respectively 100.40%, 57.96%, and 22.62% higher than that of V. natans with no R. aquatilis. The concentration of As in V. natans was increased with the increasing the As concentration up to 1 mg/L, but it was decreased at 2 mg/L As. The correlation analysis showed that the As accumulated in the plant was positive correlated (R = 0.977, p < 0.01) with indole-3-acetic acid (IAA) produced by R. aquatilis under different As levels. IAA may be the major factor affecting the As accumulation of V. natans. The results of malondialdehyde and superoxide dismutase, hydrogen peroxidase, and ascorbate peroxidase indicated that IAA produced by R. aquatilis had alleviated the arsenic stress on V. natans. The synthesis of IAA by R. aquatilis was related to the As levels. When the As was at 2 mg/L, the IAA that produced by R. aquatilis decreased and the promotion of R. aquatilis on As accumulation by V. natans reduced. However, R. aquatilis has a positive influence on the arsenic accumulation by V. natans at the lower As levels (< 2 mg/L), and it may be a potentially useful way to improve the removal of arsenic from contaminated water using submerged plants.
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http://dx.doi.org/10.1007/s11356-021-13868-9DOI Listing
April 2021

Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia.

Gen Psychiatr 2021 29;34(2):e100423. Epub 2021 Mar 29.

Department of Biochemistry and Psychopharmacology, Shanghai Mental Health Center, Shanghai, China.

Background: Aripiprazole (ARI) is often prescribed alone or in combination with other second-generation antipsychotics (SGAs) to treat patients with schizophrenia. However, this may increase the potential clinical significance of drug-drug interactions. Therapeutic drug monitoring (TDM) is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics, adjust the dosage and thereby achieve more effective and safer treatment.

Aims: This study retrospectively investigated the effects of four SGA comedications (clozapine, risperidone, quetiapine (QTP) and olanzapine) and other potential factors (sex, age and ARI dose) on the serum concentrations of ARI and dehydroaripiprazole (DARI) in Chinese patients with schizophrenia using TDM data.

Methods: High-performance liquid chromatography was used to test the serum concentrations of ARI, DARI and ARI+DARI. In addition, steady-state dose-adjusted serum concentrations (ie, concentration-to-dose ratios, C:D ratios) of ARI, DARI and ARI+DARI; sex; age; ARI dose and SGA comedication dose between 299 inpatients with schizophrenia who received ARI or SGA comedication were all collected and analysed. Spearman's correlation and multiple linear regression analysis were used to evaluate bivariate associations between ARI dose and serum ARI and DARI concentrations and describe the effect of independent variables on serum ARI and DARI concentrations, respectively.

Results: There were significant differences in the C:D ratios of ARI (χ=-3.21, p=0.001) and ARI+DARI (χ=-2.50, p=0.01) between the ARI and SGA groups, as well as in the C:D ratios of ARI (χ=-3.59, p<0.001) and ARI+DARI (χ=-3.10, p=0.002) between the female patients in the two groups. Of the four SGAs, only QTP had significant effects on the C:D ratios of ARI (Z=-4.12, p<0.001) and ARI+DARI (Z=-3.62, p<0.001) when compared with the ARI group in the whole sample and on the C:D ratios of ARI, DARI and ARI+DARI (Z=-3.96, p0.001; Z=-2.22, p=0.03; Z=-3.75, p<0.001, respectively) in women when compared with their counterparts in the ARI group.

Conclusion: Comedication with SGAs resulted in lower C:D ratios of ARI and ARI+DARI compared with ARI monotherapy, and comedication with QTP resulted in lower C:D ratios of ARI and ARI+DARI than ARI monotherapy. Despite this statistical significance of our findings, whether the presently observed effect has clinical significance requires exploration by further research. TDM and dosage regulation of ARI should be performed in Chinese inpatients with schizophrenia who are receiving SGA comedication (especially QTP) to maintain a safe and effective dose-adjusted serum concentration of ARI and DARI.
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http://dx.doi.org/10.1136/gpsych-2020-100423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009217PMC
March 2021

Common variants in CREB1 gene confer risk for bipolar disorder in Han Chinese.

Asian J Psychiatr 2021 May 6;59:102648. Epub 2021 Apr 6.

Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Recently, we have identified involvement of the gene encoding cAMP responsive element-binding 1 (CREB1) in risk of BD in European ancestry. CREB1 has significant genetic diversity between Europeans and Chinese, thereby resulting in diverged CREB1 genetic backgrounds. In this study, we aimed to determine whether CREB1 confers susceptibility to BD and cognitive dysfunction in Han Chinese. We recruited 572 patients with BD and 611 healthy controls for genetic study. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used for cognitive evaluation. SNP rs10932201 and rs3770704 within CREB1 were genotyped. The frequency of the G allele of rs10932201 was significantly greater in BD patients (41.8 %) than that in control subjects (37.2 %), with P = 0.02, corrected P = 0.04. There were significant differences in the scores of RBANS attention and total scores between the patients with different genotypes of rs10932201 polymorphism (P = 0.002 and 0.003, corrected P = 0.012 and 0.018, respectively). Post-hoc comparisons showed that rs10932201 G/G or G/A carriers had lower RBANS attention and total scores than those with A/A carriers (P = 0.002 and 0.004, P = 0.002 and 0.006, respectively). We observed a significant association between the rs10932201 and CREB1 expression in intralobular white matter (P = 0.037). Carriers with G allele have significantly lower levels of CREB1 expression in intralobular white matter than those without G allele. In conclusion, this study identified a novel BD risk SNP rs10932201 in Han Chinese and this SNP may be a risk factor for cognitive dysfunction in patients with BD.
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http://dx.doi.org/10.1016/j.ajp.2021.102648DOI Listing
May 2021

Effects of Dietary Alteration on the Gut Microbiome and Metabolome of the Rescued Bengal Slow Loris.

Front Microbiol 2021 24;12:650991. Epub 2021 Mar 24.

College of Life Science, Sichuan Agricultural University, Yaan, China.

Bengal slow lorises () are threatened by illegal trade. Subsequently, numerous wild-born individuals are rescued and transferred to rescue centers. Metabonomic analysis of intestinal microbiomes has increasingly played a vital role in evaluating the effects of dietary alteration on the captive status of endangered non-human primates. A synthetic analysis was done to test the differences in gut microbes and fecal metabolites between two dietary groups of Bengal slow lorises across 8 weeks. Dietary interventions led to intra-group convergence and inter-group variation in the composition of intestinal flora, metabolites, and short-chain fatty acids (SCFAs). The control diet, consisting of gums and honey, significantly increased the abundance of some potential probiotics, such as and , and the concentration of some anti-disease related metabolites. The decrease in some amino acid metabolites in the original group fed without gums was attributed to poor body condition. Some distinct SCFAs found in the control group indicated the dietary alteration herein was fat-restricted but fiber deficient. Cognizant of this, plant exudates and fiber-enriched food supplies should be considered an optimal approach for dietary improvement of the confiscated and captive Bengal slow lorises.
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http://dx.doi.org/10.3389/fmicb.2021.650991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024692PMC
March 2021

Discovery of effective phosphodiesterase 2 inhibitors with antioxidant activities for the treatment of Alzheimer's disease.

Bioorg Med Chem Lett 2021 Apr 8;41:128016. Epub 2021 Apr 8.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.

The multi-target-directed-ligand (MTDL) strategy has been widely applied in the discovery of novel drugs for the treatment of Alzheimer's disease (AD) because of the multifactorial pathological mechanisms of AD. Phosphodiesterase-2 (PDE2) has been identified to be a novel and promising target for AD. However, MTDL combining with the inhibitory activity against PDE2A and other anti-AD factors such as antioxidants has not been developed yet. Herein, a novel series of PDE2 inhibitors with antioxidant capacities were designed, synthesized, and evaluated. Most compounds showed remarkable inhibitory activities against PDE2A as well as antioxidant activities. Compound 6d was selected, which showed good IC of 6.1 nM against PDE2A, good antioxidant activity (ORAC (Trolox) = 8.4 eq.) and no cytotoxicity to SH-SY5Y cells. Molecular docking and dynamics simulations were applied for the rational design and explanation of structure-activity relationship (SAR) of lead compounds.
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http://dx.doi.org/10.1016/j.bmcl.2021.128016DOI Listing
April 2021

An unusual case of neck pain: Crowned-Dens Syndrome.

Rheumatology (Oxford) 2021 Apr 9. Epub 2021 Apr 9.

Rheumatology Department, Addenbrooke's Hospital, Cambridge, United Kingdom.

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http://dx.doi.org/10.1093/rheumatology/keab336DOI Listing
April 2021

VvHDZ28 positively regulate salicylic acid biosynthesis during seed abortion in Thompson Seedless.

Plant Biotechnol J 2021 Apr 9. Epub 2021 Apr 9.

College of Horticulture, Northwest A&F University, Yangling, China.

Seedlessness in grapes is one of the features most appreciated by consumers. However, the mechanisms underlying seedlessness in grapes remain obscure. Here, we observe small globular embryos and globular embryos in Pinot Noir and Thompson Seedless from 20 to 30 days after flowering (DAF). From 40 to 50 DAF, we observe torpedo embryos and cotyledon embryos in Pinot Noir but aborted embryos and endosperm in Thompson Seedless. Thus, RNA-Seq analyses of seeds at these stages from Thompson Seedless and Pinot Noir were performed. A total of 6442 differentially expressed genes were identified. Among these, genes involved in SA biosynthesis, VvEDS1 and VvSARD1, were more highly expressed in Thompson Seedless than in Pinot Noir. Moreover, the content of endogenous SA is at least five times higher in Thompson Seedless than in Pinot Noir. Increased trimethylation of H3K27 of VvEDS1 and VvSARD1 may be correlated with lower SA content in Pinot Noir. We also demonstrate that VvHDZ28 positively regulates the expression of VvEDS1. Moreover, over-expression of VvHDZ28 results in seedless fruit and increased SA contents in Solanum lycopersicum. Our results reveal the potential role of SA and feedback regulation of VvHDZ28 in seedless grapes.
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http://dx.doi.org/10.1111/pbi.13596DOI Listing
April 2021