Publications by authors named "Pan Li"

1,470 Publications

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Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery.

Microb Biotechnol 2022 May 16. Epub 2022 May 16.

Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.

The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non-profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm microbiota precipitation (1.0 × 10 bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.
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http://dx.doi.org/10.1111/1751-7915.14074DOI Listing
May 2022

Inductive stimuli of the startle response and critical points of psychological treatment in a severe burn patient.

J Burn Care Res 2022 May 16. Epub 2022 May 16.

Doctor of Psychiatry, Chengdu Medical College, Sichuan Province, China.

Severe burn patients often have anxiety, depression, and stress-related disorders. The case we reported was very nervous and exhibited a long-term high-frequency startle response, which disrupted his sleep seriously and decreased treatment compliance. However, after psychological treatment, his startle response in the daytime and nervousness gradually improved, but the startle response at night remained unchanged. Furthermore, after his wife was given three sessions of psychological treatment to manage her fear of surgery, the startle response at night was significantly reduced. Herein, we summarize the inductive stimuli of the startle response and the critical points of psychological treatment in this case to provide the clinical experience for future research.
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http://dx.doi.org/10.1093/jbcr/irac066DOI Listing
May 2022

Homologous Recombination Related Signatures Predict Prognosis and Immunotherapy Response in Metastatic Urothelial Carcinoma.

Front Genet 2022 26;13:875128. Epub 2022 Apr 26.

Department of Urology, Lanzhou University Second Hospital, Lanzhou, China.

This study used homologous recombination (HR) related signatures to develop a clinical prediction model for screening immune checkpoint inhibitors (ICIs) advantaged populations and identify hub genes in advanced metastatic urothelial carcinoma. The single-sample gene enrichment analysis and weighted gene co-expression network analysis were applied to identify modules associated with immune response and HR in IMvigor210 cohort samples. The principal component analysis was utilized to determine the differences in HR-related module gene signature scores across different tissue subtypes and clinical variables. Risk prediction models and nomograms were developed using differential gene expression analysis associated with HR scores, least absolute shrinkage and selection operator, and multivariate proportional hazards model regression. Additionally, hub genes were identified by analyzing the contribution of HR-related genes to principal components and overall survival analysis. Finally, clinical features from GSE133624, GSE13507, the TCGA, and other data sets were analyzed to validate the relationship between hub genes and tumor growth and mutation. The HR score was significantly higher in the complete/partial response group than in the stable/progressive disease group. The majority of genes associated with HR were discovered to be involved in the cell cycle and others. Genomically unstable, high tumor level, and high immune level samples all exhibited significantly higher HR score than other sample categories, and higher HR scores were related to improved survival following ICIs treatment. The risk scores for , , , , , and were identified, and the training and verification groups had markedly different survival times. The risk score, tumor neoantigen burden, mismatch repair, and cell cycle regulation were discovered to be independent predictors of survival time following immunotherapy. Patients with a high level of expression of hub genes such as , , and had a greater chance of surviving following immunotherapy. These genes are expressed at significantly higher levels in tumors, high-grade cancer, and invasive cancer than other categories, and are associated with TP53 and RB1 mutations. HR-related genes are upregulated in genomically unstable samples, the survival time of mUC patients after treatment with ICIs can be predicted using a normogram model based on HR signature.
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http://dx.doi.org/10.3389/fgene.2022.875128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086193PMC
April 2022

Supramolecular Proton Conductors Self-Assembled by Organic Cages.

JACS Au 2022 Apr 21;2(4):819-826. Epub 2022 Mar 21.

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Proton conduction is vital for living systems to execute various physiological activities. The understanding of its mechanism is also essential for the development of state-of-the-art applications, including fuel-cell technology. We herein present a bottom-up strategy, that is, the self-assembly of and with an identical chemical composition but distinct structural features to provide two different supramolecular conductors that are ideal for the mechanistic study. with a larger cavity size and more H-bonding anchors self-assembled into a crystalline phase with more proton hopping pathways formed by H-bonding networks, where the proton conduction proceeded via the Grotthuss mechanism. Small cavity-sized with less H-bonding anchors formed the crystalline phase with loose channels filled with discrete H-bonding clusters, therefore allowing for the translational diffusion of protons, that is, vehicle mechanism. As a result, the former exhibited a proton conductivity of 1.59 × 10 S/cm at 303 K under a relative humidity of 48%, approximately 200-fold higher compared to that of the latter. Ab initio molecular dynamics simulations revealed distinct H-bonding dynamics in and , which provided further insights into potential proton diffusion mechanisms. This work therefore provides valuable guidelines for the rational design and search of novel proton-conducting materials.
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http://dx.doi.org/10.1021/jacsau.1c00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089675PMC
April 2022

Construction of Ag [email protected] nanoparticle nano nests with densely stacked small gaps for actively trapping molecules to realize diversity SERS detection.

Analyst 2022 May 12. Epub 2022 May 12.

Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Highly sensitive surface-enhanced Raman spectroscopy (SERS) sensing not only depends on an active substrate with high density of hot spots, but also depends more on whether the molecules can effectively enter the hot spot region. In this paper, a new SERS detection method based on the nano nest model is developed to autonomously capture molecules into hot spots. The nano nest is composed of silver nanowires modified with gold nanoparticles (Ag [email protected] NPs), which not only form high density hot spots between particles or particles-wires, but also have a coupled electromagnetic field enhancement effect. The SERS detection method based nano nest actively traps molecules through the capillary stage, and makes the molecules move toward densely stacked small gaps (hot spots) by capillary action. The above method has been used to detect different kinds of molecules, such as pesticide residues, adenosine triphosphate in culture medium, and antibiotic residues in aquatic products. In addition, an SERS monitoring of allergic reactions was also performed using nano nests with the feature of actively trapping molecules into the hot spots. This nano nest will be able to perform a direct monitoring of biochemical reactions, and more importantly, it can provide a new scheme for SERS detection.
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http://dx.doi.org/10.1039/d2an00527aDOI Listing
May 2022

Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in .

Front Microbiol 2022 25;13:845173. Epub 2022 Apr 25.

Department of Pediatrics and Department of Allergy, The Third Affiliated Hospital, State Key Laboratory of Bio-Control, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou, China.

Antibiotic-resistant is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography-mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant strains that originated from ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16, PA-R64, and PA-R128, respectively) higher than the original value, compared to CIP-sensitive (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128 and clinically multidrug-resistant strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of and provide a target pathway for combating CIP-resistant .
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http://dx.doi.org/10.3389/fmicb.2022.845173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083408PMC
April 2022

The enhanced conservation of vital pulp and apical tissues by the application of crown rotation surgery for inversely impacted central incisors: a follow-up analysis of two patients over four years.

Int Endod J 2022 May 11. Epub 2022 May 11.

Department of Operative Dentistry and Endodontics, School of Stomatology, FMMU, Xi'an, 710032, China.

Aim: To describe a novel surgical method (crown rotation surgery) to manage inversely impacted central incisors with immature roots.

Summary: Two young patients each presented with an inversely impacted maxillary central incisor. To protect the apical tissues, the two impacted incisors were rotated downwards to a relatively normal position without extraction from their bony sockets. After crown rotation surgery, spontaneous eruption, continuous root development, and periodontal healing of the rotated incisors were observed. The pulp retained vitality and blood flow was normal. Moreover, there were no obvious signs of pulp canal obliteration (PCO), as indicated by Cone Beam Computed Tomography (CBCT) imaging.

Key Learning Points: • By optimising protection of the vital pulp and apical tissues, crown rotation surgery represents a minimally invasive, conservative, and practical surgical technique for treating inversely impacted incisors with developing roots. • In contrast to existing surgical methods, crown rotation surgery may avoid certain complications, including PCO and abnormal or arrested root development.
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http://dx.doi.org/10.1111/iej.13761DOI Listing
May 2022

Anti-IL-8 antibody activates myeloid cells and potentiates the anti-tumor activity of anti-PD-1 antibody in the humanized pancreatic cancer murine model.

Cancer Lett 2022 Jul 7;539:215722. Epub 2022 May 7.

The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Department of Surgery, and the Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14 and CD16 myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16 myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response.
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http://dx.doi.org/10.1016/j.canlet.2022.215722DOI Listing
July 2022

An overlooked dispersal route of Cardueae (Asteraceae) from the Mediterranean to East Asia revealed by phylogenomic and biogeographic analyses of Atractylodes.

Ann Bot 2022 May 9. Epub 2022 May 9.

Systematic & Evolutionary Botany and Biodiversity Group, MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.

Background And Aims: The East Asian-Tethyan disjunction pattern and its formation mechanisms have long been of interest to researchers. Here, we studied the biogeographic history of Asteraceae tribe Cardueae, with a particular focus on the temperate East Asian genus Atractylodes DC., to understand the role of tectonic and climatic events in driving the diversification and disjunctions of the genus.

Methods: A total of 76 samples of Atractylodes from 36 locations were collected for the RAD-seq. Three SNP datasets based on different filtering strategies were used for phylogenetic analyses. Molecular dating and ancestral distribution reconstruction were performed using both cpDNA sequences (127 Cardueae samples) and SNP (36 Atractylodes samples) datasets.

Key Results: Six species of Atractylodes were well resolved as individually monophyletic, although some introgression was identified among accessions of A. chinensis, A. lancea and A. koreana. Dispersal of the subtribe Carlininae from the Mediterranean to East Asia occurred after divergence between Atractylodes and Carlina L. + Atractylis L. + Thevenotia DC. at c. 31.57 Ma, resulting in an East Asian-Tethyan disjunction. Diversification of Atractylodes in East Asia mainly occurred from the Late Miocene to the Early Pleistocene.

Conclusions: Aridification of Asia and the closure of the Turgai Strait in the Late Oligocene promoted the dispersal of Cardueae from the Mediterranean to East China. Subsequent uplift of QTP as well as changes in Asian monsoon systems resulted in an East Asian-Tethyan disjunction between Atractylodes and Carlina + Atractylis + Thevenotia. In addition, Late Miocene to Quaternary climates and sea level fluctuations played major roles in the diversification of Atractylodes. Through this study of different taxonomic levels using genomic data, we have revealed an overlooked dispersal route between the Mediterranean and far East Asia (Japan/Korea) via Central Asia and East China.
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http://dx.doi.org/10.1093/aob/mcac059DOI Listing
May 2022

Genomic Data Sharing under Dependent Local Differential Privacy.

CODASPY 2022 Apr 15;2022:77-88. Epub 2022 Apr 15.

Case Western Reserve University, Cleveland, Ohio.

Privacy-preserving genomic data sharing is prominent to increase the pace of genomic research, and hence to pave the way towards personalized genomic medicine. In this paper, we introduce (, )-dependent local differential privacy (LDP) for privacy-preserving sharing of correlated data and propose a genomic data sharing mechanism under this privacy definition. We first show that the original definition of LDP is not suitable for genomic data sharing, and then we propose a new mechanism to share genomic data. The proposed mechanism considers the correlations in data during data sharing, eliminates statistically unlikely data values beforehand, and adjusts the probability distributions for each shared data point accordingly. By doing so, we show that we can avoid an attacker from inferring the correct values of the shared data points by utilizing the correlations in the data. By adjusting the probability distributions of the shared states of each data point, we also improve the utility of shared data for the data collector. Furthermore, we develop a greedy algorithm that strategically identifies the processing order of the shared data points with the aim of maximizing the utility of the shared data. Our evaluation results on a real-life genomic dataset show the superiority of the proposed mechanism compared to the randomized response mechanism (a widely used technique to achieve LDP).
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http://dx.doi.org/10.1145/3508398.3511519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9073402PMC
April 2022

Intelligent and robust DNA robots capable of swarming into leakless nonlinear amplification in response to a trigger.

Nanoscale Horiz 2022 May 9. Epub 2022 May 9.

Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui, China.

Nonlinear DNA signal amplification with an enzyme-free isothermal self-assembly process is uniquely useful in nanotechnology and nanomedicine. However, progress in this direction is hampered by the lack of effective design models of leak-resistant DNA building blocks. Here, we propose two conceptual models of intelligent and robust DNA robots to perform a leakless nonlinear signal amplification in response to a trigger. Two conceptual models are based on super-hairpin nanostructures, which are designed by innovating novel principles in methodology and codifying them into embedded programs. The dynamical and thermodynamical analyses reveal the critical elements and leak-resistant mechanisms of the designed models, and the leak-resistant behaviors of the intelligent DNA robots and morphologies of swarming into nonlinear amplification are separately verified. The applications of the designed models are also illustrated in specific signal amplification and targeted payload enrichment integration with an aptamer, a fluorescent molecule and surface-enhanced Raman spectroscopy. This work has the potential to serve as design guidelines of intelligent and robust DNA robots and leakless nonlinear DNA amplification, and also as the design blueprint of cargo delivery robots with the performance of swarming into nonlinear amplification in response to a target automatically, facilitating their future applications in biosensing, bioimaging and biomedicine.
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http://dx.doi.org/10.1039/d2nh00018kDOI Listing
May 2022

Nasal secretion tissue plasminogen activator, a novel effective predictor of nasal polyp recurrence.

J Allergy Clin Immunol Pract 2022 May 5. Epub 2022 May 5.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2022.04.031DOI Listing
May 2022

Association of Egg Consumption with Risk of All-Cause and Cardiovascular Disease Mortality: A Systematic Review and Dose-Response Meta-analysis of Observational Studies.

J Nutr 2022 May 7. Epub 2022 May 7.

Department of Epidemiology and Health Statistics, School of Public Health, Shenzhen University Health Science Center.

Background: Recent studies have reported conflicting associations between egg consumption and the risk of all-cause or cardiovascular disease (CVD) mortality, including ischemic heart disease (IHD) mortality and stroke mortality. With accumulating evidence, up-to-date evidence about the association should be synthesized.

Objective: To assess the association of the risk of all-cause and CVD mortality with egg consumption.

Methods: We searched PubMed, EMBASE, and Web of Science databases through November 3, 2021 for observational studies conducted in participants ≥18 y of age and provided ORs or RRs or HRs and 95% CIs for ≥3 egg consumption categories or for increased intake of egg with the associations of interest. Random-effects model was used to pool the reported risk estimates. Restricted cubic splines were used to examine the dose-response association.

Results: Twenty-four articles with 48 reports (25 for all-cause mortality, 11 for CVD mortality, 6 for IHD mortality, and 6 for stroke mortality) involving 11,890,695 participants were included. Intake of each 1 egg/day increment was associated with increased risk of all-cause mortality (RR 1.06; 95% CI 1.02, 1.10; P = 0.008), but the association was restricted to women, Americans, and studies with adjustments for hyperlipidemia. Egg consumption was linearly associated with CVD mortality only in participants >60 y of age, Americans, studies with follow-up duration≥15 years, and adjustments for hyperlipidemia (P ≤0.018). No significant association was found between egg consumption and IHD or stroke mortality (P ≥0.080).

Conclusions: Egg consumption was linearly associated with a modestly risk of all-cause mortality and, in older participants, Americans, studies with longer follow-up or adjustments for hyperlipidemia, CVD mortality. These findings suggest that it may be prudent to avoid high egg consumption.
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http://dx.doi.org/10.1093/jn/nxac105DOI Listing
May 2022

ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling.

J Nanobiotechnology 2022 May 6;20(1):213. Epub 2022 May 6.

Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-β (TGF-β), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-β expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation.

Results: We synthesized DMF-loaded ROS-responsive [email protected] liposomes ([email protected] NPs). [email protected] NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while [email protected] NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that [email protected] NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-β and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, [email protected] NPs treatment presented enhanced antifibrotic effect. [email protected] NPs also had a prolonged residence time in the lung as well as excellent biocompatibility.

Conclusions: [email protected] NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.
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http://dx.doi.org/10.1186/s12951-022-01435-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074278PMC
May 2022

Genome-wide analyses of introgression between two sympatric Asian oak species.

Nat Ecol Evol 2022 May 5. Epub 2022 May 5.

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

Introgression can be an important source of new alleles for adaption under rapidly changing environments, perhaps even more important than standing variation. Though introgression has been extensively studied in many plants and animals, key questions on the underlying mechanisms of introgression still remain unanswered. In particular, we are yet to determine the genomic distribution of introgressed regions along the genome; whether the extent and patterns of introgression are influenced by ecological factors; and when and how introgression contributes to adaptation. Here, we generated high-quality genomic resources for two sympatric widespread Asian oak species, Quercus acutissima and Q. variabilis, sampled in multiple forests to study introgression between them. We show that introgressed regions are broadly distributed across the genome. Introgression was affected by genetic divergence between pairs of populations and by the similarity of the environments in which they live-populations occupying similar ecological sites tended to share the same introgressed regions. Introgressed genomic footprints of adaptation were preferentially located in regions with suppressed recombination rate. Introgression probably confers adaptation in these oak populations by introducing allelic variation in cis-regulatory elements, in particular through transposable element insertions, thereby altering the regulation of genes related to stress. Our results provide new avenues of research for uncovering mechanisms of adaptation due to hybridization in sympatric species.
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http://dx.doi.org/10.1038/s41559-022-01754-7DOI Listing
May 2022

Atomistic mechanism of phase transformation between topologically close-packed complex intermetallics.

Nat Commun 2022 May 5;13(1):2487. Epub 2022 May 5.

Institute of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing, 100124, China.

Understanding how topologically close-packed phases (TCPs) transform between one another is one of the challenging puzzles in solid-state transformations. Here we use atomic-resolved tools to dissect the transition among TCPs, specifically the μ and P (or σ) phases in nickel-based superalloys. We discover that the P phase originates from intrinsic (110) faulted twin boundaries (FTB), which according to first-principles calculations is of extraordinarily low energy. The FTB sets up a pathway for the diffusional in-flux of the smaller 3d transition metal species, creating a Frank interstitial dislocation loop. The climb of this dislocation, with an unusual Burgers vector that displaces neighboring atoms into the lattice positions of the product phase, accomplishes the structural transformation. Our findings reveal an intrinsic link among these seemingly unrelated TCP configurations, explain the role of internal lattice defects in facilitating the phase transition, and offer useful insight for alloy design that involves different complex phases.
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http://dx.doi.org/10.1038/s41467-022-30040-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072387PMC
May 2022

ESR1 mediates estrogen-induced feminization of genetic male Chinese soft-shelled turtle.

Biol Reprod 2022 May 3. Epub 2022 May 3.

Institute of Animal Sex and Development, Zhejiang Wanli University, Ningbo, 315100, China.

Exogenous estrogen have shown their femininization abilities during the specific sex differentiation period in several reptiles. However, the specific regulatory mechanism and downstream regulatory genes of estrogen remain elusive. In the present study, 17β-estradiol (E2), as well as drugs of specific antagonists and/or agonists of estrogen receptors, were employed to figure out the molecular pathway involved in the E2-induced feminization in Chinese soft-shelled turtles, an important aquaculture species in China. E2 treatment led to typical female characteristics in the gonads of ZZ individuals, including thickened outer cortex containing a number of germ cells and degenerated medullary cords, as well as the disappearance of male marker SOX9, and the ectopic expression of ovarian regulator FOXL2 at the embryonic developmental stage 27 and 1 month after hatching. The specific ESR1 antagonist or a combination of three estrogen receptor antagonists could block the sex reversal of ZZ individuals induced by estrogen. In addition, specific activation of ESR1 by agonist also led to the feminization of ZZ gonads, which was similar to the effect of estrogen treatment. Furthermore, transcriptome data showed that the expression level of FOXL2 was significantly up-regulated, while mRNA levels of DMRT1, SOX9 and AMH were down-regulated after estrogen treatment. Taken together, our results indicated that E2 induced the feminization of ZZ Chinese soft-shelled turtles via ESR1, and decrease of male genes DMRT1, SOX9and AMH and increase of ovarian development regulator FOXL2 might be responsible for the initiation of E2-induced feminization.
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http://dx.doi.org/10.1093/biolre/ioac088DOI Listing
May 2022

SP1-mediated up-regulation of lncRNA TUG1 underlines an oncogenic property in colorectal cancer.

Cell Death Dis 2022 May 4;13(5):433. Epub 2022 May 4.

Department of General Surgery, Yan'an People's Hospital, Yan'an, 716000, P.R. China.

The long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) acts as tumor-promoting factor in colorectal cancer (CRC). We aimed to elucidate the mechanism by which the transcription factor specificity protein 1 (SP1) regulates TUG1 and microRNAs (miRs)/mRNAs in the context of CRC, which has not been fully studied before. Expression patterns of TUG1 and SP1 were determined in clinical CRC samples and cells, followed by identification of their interaction. Next, the functional significance of TUG1 in CRC was investigated. An in vivo CRC model was established to validate the effect of TUG1. The results demonstrated that TUG1 and SP1 were highly-expressed in CRC, wherein SP1 bound to the TUG1 promoter and consequently, positively regulated its expression. Silencing of TUG1 caused suppression of CRC cell growth and promotion of cell apoptosis. TUG1 could bind to miR-421 to increase KDM2A expression, a target gene of miR-421. TUG1 could activate the ERK pathway by impairing miR-421-targeted inhibition of KDM2A. Additionally, SP1 could facilitate the tumorigenesis of CRC cells in vivo by regulating the TUG1/miR-421/KDM2A/ERK axis. Altogether, the current study emphasizes the oncogenic role of TUG1 in CRC, and illustrates its interactions with the upstream transcription factor SP1 and the downstream modulatory axis miR-421/KDM2A/ERK, thus offering novel insights into the cancerogenic mechanism in CRC.
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http://dx.doi.org/10.1038/s41419-022-04805-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068916PMC
May 2022

Gene Polymorphisms Interact With the Urbanized Living Environment on Obesity: Results From the Yi Migrant Study.

Front Genet 2022 14;13:849138. Epub 2022 Apr 14.

Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

This study aimed to determine the association of gene polymorphisms (rs17782313 and rs12970134) and urbanized living environment and the gene-environment interaction with obesity in Yi people in China. A 1:2 frequency-matched case-control study based on the cross-sectional data was designed. Those with BMI ≥28 kg/m were included as the case group. The age- and sex-matched controls were selected from those with BMI <24 kg/m. Unconditional logistic models were used to determine the association of SNPs with obesity. Additive interaction was evaluated by calculating relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). A total of 322 cases and 643 controls were included. After adjustment, allele C of rs17782313 was significantly associated with obesity (additive model, OR = 1.52, 95%CI: 1.18-1.96) in Yi people. A similar association was found in allele A of rs12970134 (additive model, OR = 1.45, 95%CI: 1.13-1.89). Yi rural-to-urban migrants were found at 2.59-fold (95%CI: 1.70-3.95) higher odds of obesity than Yi farmers. Additive interactions were found between the two SNPs and rural-to-urban migration (rs17782313: AP = 0.65, 95%CI: 0.22-1.09; rs12970134: AP = 0.59, 95%CI: 0.02-1.17). gene polymorphisms positively interacted with the urbanized living environment on obesity in Yi people. The effect of the gene on obesity was modified by the living environment.
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http://dx.doi.org/10.3389/fgene.2022.849138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046839PMC
April 2022

Effect of NaCl addition on alcohol-alkali-treated waxy rice starch: Structural and physicochemical functionality.

Food Chem 2022 Apr 21;389:133021. Epub 2022 Apr 21.

College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address:

The physicochemical and structural properties of waxy rice starch (WRS) and alcohol-alkali-treated waxy rice starch (AAT-WRS) were determined in the presence of different concentrations of NaCl (0, 2, 4, 6 and 8%). The results showed that NaCl decreased the transparency of WRS and AAT-WRS pastes, but enhanced both freeze-thaw stability and apparent viscosity (p < 0.05). The rheological measurement results showed that the addition of NaCl could improve the modulus values of both WRS and AAT-WRS, and the effect on WRS was more significant than that on AAT-WRS. The textural parameters of WRS pastes were evidently enhanced by NaCl, but the presence of NaCl had no significant effect on the firmness of AAT-WRS pastes. The results of SEM and FT-IR revealed that NaCl could protect the granular morphology and increase the degree of short-range order of WRS and AAT-WRS.
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http://dx.doi.org/10.1016/j.foodchem.2022.133021DOI Listing
April 2022

Grafting of thermotropic fluorinated mesogens on polysiloxane to improve the processability of linear low-density polyethylene.

RSC Adv 2022 Apr 25;12(20):12463-12470. Epub 2022 Apr 25.

Center for Molecular Science and Engineering, Northeastern University Shenyang 110819 China.

In this study, a series of polysiloxane grafted with thermotropic fluorinated mesogens (TSCPFLCP) is designed and synthesized. The TSCPFLCP exhibits a typical smectic liquid crystal phase, and shows a high thermal decomposition temperature at 335.6 °C. After blending with LLDPE, the balance melt torque of LLDPE/TSCPFLCP is decreased by 42% at 0.5 wt% TSCPFLCP, and the corresponding power law index is increased to 0.45. The flowing activation energy of the optimized LLDPE/TSCPFLCP blend is lower than that of pure LLDPE at the same shear rate, indicating that TSCPFLCP reduced the sensitivity of the apparent melt viscosity of LLDPE to both shear rate and temperature. This contributes to the broadening of the LLDPE processing window. On the other hand, TSCPFLCP is also found beneficial in ameliorating melt fracture during LLDPE extrusion. Furthermore, the mechanical properties of LLDPE/TSCPFLCP blends, such as tensile strength, elastic modulus and elongation at break, are also enhanced significantly at 0.5 wt% TSCPFLCP. Altogether, TSCPFLCP has been proven an effective processing aid to improve the processability and toughness of LLDPE.
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http://dx.doi.org/10.1039/d2ra01482cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036815PMC
April 2022

, a New Species of Smilacaceae from Limestone Areas Bordering Guizhou and Guangxi, China.

Plants (Basel) 2022 Apr 11;11(8). Epub 2022 Apr 11.

Laboratory of Systematic & Evolutionary Botany and Biodiversity, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

A new species, (Smilacaceae), from Southwest China, is described and illustrated. The new species bears peltate leaves, which was previously a unique feature of . However, it differs from the latter by having a broad ovate leaf blade, longer peduncle, and sexual dimorphic flowers. Further phylogenetic analyses revealed that the new species were placed in a unique position in a subclade of Old World based on ptDNA and nrITS sequences. Combining detailed morphological comparisons and molecular evidence, we validated that is an undescribed new species. Moreover, the plastome characteristics of are reported.
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http://dx.doi.org/10.3390/plants11081032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028124PMC
April 2022

Heterologous Synthesis of Monacolin J by Reconstructing Its Biosynthetic Gene Cluster in .

J Fungi (Basel) 2022 Apr 16;8(4). Epub 2022 Apr 16.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou Higher Education Mega Center, Panyu Town, Guangzhou 510006, China.

Monacolin J (MJ), a key precursor of Lovastatin, could synthesize important statin drug simvastatin by hydrolyzing lovastatin and adding different side chains. In this study, to reduce the cumbersome hydrolysis of lovastatin to produce MJ in the native strain , the MJ biosynthetic pathway genes (, , and ) were heterologously integrated into the genome of CBS513.88 with strong promoters and suitable integration sites, via yeast 2μ homologous recombination to construct expression cassettes of long-length genes and CRISPR/Cas9 homology-directed recombination (CRISPR-HDR) to integrate MJ genes in the genome of . RT-PCR results proved that pathway synthesis-related genes could be heterologously expressed in . Finally, we constructed an engineered strain that could produce monacolin J, detected by LC-HR-ESIMS (MJ, 339.22 [M-H]). The yield of MJ reached 92.90 mg/L after 7-day cultivation. By optimizing the cultivation conditions and adding precursor, the final titer of MJ was 142.61 mg/L on the fourth day of fed-batch cultivation, which was increased by 53.5% compared to the original growth conditions. Due to the wide application of in industrial fermentation for food and medicine, the following work will be dedicated to optimizing the metabolic network to improve the MJ production in the engineered strain.
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http://dx.doi.org/10.3390/jof8040407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032219PMC
April 2022

Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at the First Recurrence: A Preliminary Report.

Brain Sci 2022 Apr 2;12(4). Epub 2022 Apr 2.

CyberKnife Center, Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Road (M), Shanghai 200040, China.

(1) Background: Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies have been reported to have a promising survival benefit in recent studies. Anlotinib is a new oral VEGF receptor inhibitor. This report describes our experience using HSRT and anlotinib for recurrent glioblastoma (rGBM). (2) Methods: Between December 2019 and June 2020, rGBM patients were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. (3) Results: Five patients were enrolled. The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 21 (14-33). The ORR was 100%. Three (60%) patients had the best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). One patient died of tumour progression at the last follow-up. Two patients had grade 2 hand-foot syndrome. (4) Conclusions: Salvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM. A prospective phase II study (NCT04197492) is ongoing to further investigate the regimen.
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http://dx.doi.org/10.3390/brainsci12040471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032064PMC
April 2022

Contamination of 16 priority polycyclic aromatic hydrocarbons (PAHs) in urban source water at the tidal reach of the Yangtze River.

Environ Sci Pollut Res Int 2022 Apr 19. Epub 2022 Apr 19.

Key Laboratory of Yangtze River Water Environment of the Ministry of Education, College of Environmental Science and Engineering, Tongji University, No. 1239 Siping Road, Shanghai, 200092, China.

To explore the occurrence, source, and risk of 16 priority polycyclic aromatic hydrocarbons (PAHs) in urban source water at the tidal reach of the Yangtze River, eighty-nine surface water samples were collected in 8 field campaigns from July 2018 to November 2019. Fifteen of 16 PAHs except for dibenz(a,h)anthracene (DBA) were found in the water. Detection frequencies were observed between 53 and 72% for PAHs with 4 rings, while most of other PAHs were less detected, e.g., benzo(a)pyrene (BaP) in 31% of samples. The total concentrations of 16 priority PAHs reached up to 2.8 µg·L and increased during the tidal transitions from flood to ebb. The average concentrations of PAHs in ebb tides were higher than those in flood tides. PAH concentrations and compositions showed great variation with different sampling campaigns, and higher levels and more components were observed in the rainy months and cold months. Those priority PAHs in the tidal water source are mainly from combustion activities (especially fossil fuel combustion), but the contribution from oil spills/leakage is also important in rainy months. High-molecular-weight PAHs in this tidal water source may pose risks to aquatic life, while they pose no carcinogenic risk to human health via ingestion of drinking water.
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http://dx.doi.org/10.1007/s11356-022-20052-0DOI Listing
April 2022

Scalable synthesis of hydroxyl-functionalized boron nanosheets for high ion-conductive solid-state electrolyte applications.

Chem Commun (Camb) 2022 May 5;58(37):5586-5589. Epub 2022 May 5.

Institute of Advanced Materials, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, P. R. China.

A hydroxyl-functionalized boron nanosheet is developed as the filler material for the solid-state electrolyte (SSE) of lithium batteries. The nanosheet exhibits good oxidation resistance and thermal stability. Its composite SSE shows high ionic conductivity, and the resulting batteries present much enhanced capacities, rate capability and cycling performance, proving the electrochemical advances of the boron nanosheet.
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http://dx.doi.org/10.1039/d2cc00690aDOI Listing
May 2022

Hydrochloride Berberine ameliorates alcohol-induced liver injury by regulating inflammation and lipid metabolism.

Biochem Biophys Res Commun 2022 Jun 7;610:49-55. Epub 2022 Apr 7.

Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address:

Aims: Berberine hydrochloride (BBR) is efficacious in relieving alcoholic liver injury (ALI) in animal models, but its underlying mechanisms remains largely unclear.

Methods And Results: In the study, the rats were divided into control group, model group, model with BBR group, and control with BBR group, and given corresponding treatment for 4 weeks. RNA-Seq, ELISA and RT-PCR were performed to explore the potential mechanisms of BBR in ALI. Treatment of rats with BBR (200 mg/kg/d, gavage, once daily) over 4 weeks diminished 4 g/kg/d alcohol-induced inflammation and lipid deposition. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in BBR-treated rats. Hepatic gene expression profile detected that BBR suppressed ethanol-stimulated overexpression of thyroid hormone responsive gene-THRSP. And overexpression of THRSP-responsive genes (fatty acid synthase-FASN, adenosine monophosphate activated protein kinase α-AMPK-α, acetyl-CoA carboxylase-ACC, ATP-citrate lyase-ACLY) responsible for fatty acid synthesis was also downregulated by BBR. Additionally, BBR downregulated expression of cluster of differentiation 36-CD36 and upregulated expression of peroxisome proliferator-activated receptor α (PPARα) and its target genes (carnitine palmitoyltransferase 1 α-CPT1α and acyl-CoA oxidase 1-ACOX1). Meanwhile, BBR treatment suppressed systemic inflammation by mediating a reduction in IL-10, TNF-α, LPS, and ET, but elevated IL-6.

Conclusions: The results indicated that BBR alleviated alcoholism-induced hepatic injury by suppressing inflammation (IL-10, TNF-α, LPS, ET and IL-6), and regulating fatty acids uptake (CD36), lipid synthesis (THRSP, FASN, AMPK-α, ACC, ACLY) and lipid oxidation (PPARα, CPT1α, ACOX1), and THRSP may be its novel target.
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http://dx.doi.org/10.1016/j.bbrc.2022.04.009DOI Listing
June 2022

Exploring the Effect of Enbrel Softgels on PWI Indicators in VCIND Patients.

J Healthc Eng 2022 6;2022:9681235. Epub 2022 Apr 6.

Department of Neurology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China.

Objective: To investigate the effect of Enbrel softgels on the head nuclear magnetic (PWI) indices in patients with vascular cognitive impairment-no dementia (vascular cognitive impairment-no dementia, VCIND).

Methods: Patients with confirmed VCIND hospitalized in the Department of Neurology of the Affiliated Hospital of Hebei University from April 2017 to April 2019 were included in the study, and they were divided into experimental and control groups (30 patients in each group) according to the difference of interventions. The PWI examination and neuropsychological assessment were performed at the beginning of the experiment, 12 w after treatment, and 48 w after treatment in the two groups. Score differences between the two groups and the preliminary demonstration of the clinical value of the MMSE and ADAS-Cog in the diagnosis of VCIND.

Results: (1) The difference in PWI positivity rate between the two groups at the beginning of the experiment was not statistically significant ( > 0.05); the PWI positivity rate in the experimental group at 12 W was significantly lower than that in the control group ( < 0.05); the difference in PWI positivity rate between the two groups at 48 W was not statistically significant ( < 0.05); (2) the MMSE scores of patients in the experimental group at 12 W and 48 W were higher than those in the control group, and the ADAS-Cog scores were lower than those in the control group ( < 0.05). (3) The diagnostic AUCs of MMSE and ADAS-Cog for VCIND were 0.7960 (95% CI = 0.6411-0.9508, =0.0037) and 0.9291 (95% CI = 0.8390), respectively (95% CI = 0.8390-1.000, < 0.0001).

Conclusion: The addition of Enbrel softgels to concomitant therapy in VCIND patients can lead to changes in their PWI imaging indicators, which in turn can have a significant impact on their neuropsychological indicators, and quantitative analysis scales such as the MMSE and ADAS-Cog can be considered for the diagnostic treatment of VCIND.
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http://dx.doi.org/10.1155/2022/9681235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007643PMC
April 2022

Baicalin ameliorates alcohol-induced hepatic steatosis by suppressing SREBP1c elicited PNPLA3 competitive binding to ATGL.

Arch Biochem Biophys 2022 Jun 13;722:109236. Epub 2022 Apr 13.

Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

Baicalin is a flavonoid compound abundant in multiple edible and medicinal plants such as Scutellaria baicalensis Georgi. In this study, we provide evidence to support the fact that baicalin ameliorates alcohol-induced hepatic steatosis via regulating SREBP1c elicited PNPLA3 competitive binding to ATGL. Results showed that baicalin significantly attenuated the development of metabolic disorders and hepatic steatosis in alcohol-induced rats after four weeks of treatment. It was evident that baicalin treatment significantly normalized the serous contents of hepatic triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and attenuated the increase of hepatic vacuolization and Oil Red O staining area caused by alcohol. Meanwhile, baicalin relieves alcohol-induced hepatic fibrosis by masson staining and RT-qPCR analysis. Mechanistically, alcohol aggravated the nuclear expression of SREBP1c, which contributed to the high expression of PNPLA3 and FASN, thereby enhancing the binding of PNPLA3 to ABHD5, and indirectly impairing the binding ability between ATGL and ABHD5, ultimately causing a decline in the hydrolysis capacity in liver lipid droplets. As expected, these alcohol-induced pathobolism were reversed by baicalin treatment both in vivo and in vitro. In conclusion, this study has demonstrated that baicalin can protect against alcohol-induced hepatic lipid accumulation by activating hepatic lipolysis via suppressing SREBP1c elicited PNPLA3 competitive binding to ATGL. Baicalin is a promising natural product for preventing alcohol-induced hepatic steatosis.
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http://dx.doi.org/10.1016/j.abb.2022.109236DOI Listing
June 2022

Chemical characterization of Wuyi rock tea with different roasting degrees and their discrimination based on volatile profiles.

RSC Adv 2021 Mar 25;11(20):12074-12085. Epub 2021 Mar 25.

Department of Tea Science, Zhejiang University Hangzhou 310058 China

Wuyi rock tea is a typical and famous oolong tea in China and roasting is an important manufacturing procedure for its flavor formation. This work aimed to explore the effect of roasting on non-volatiles and volatiles of 12 Wuyi rock tea samples at three roasting levels (low, moderate and sufficient), made from four tea cultivars (Shuixian, Qizhong, Dahongpao, Rougui). Results show that different roasting had not caused significant difference on contents of soluble solids, total polyphenols, flavonoids, soluble sugar, thearubigins and theabrownins, while it slightly regulated caffeine, proteins and theaflavins, and remarkably reduced catechins and free amino acids. The ratio of polyphenol content/amino acid content, a negative-correlated indicator of fresh and brisk taste, significantly increased with the increase of roasting degree. High-level roasting not only decreased the fresh and brisk taste of the tea infusion, but also reduced the amount of bioactive ingredients including catechins and theanine. A total of 315 volatiles were detected and analyzed with OPLS-DA and HCA methods, in which 99 volatiles were found with variable importance in the projection (VIP) values greater than 1.00. Tea samples at different roasting degrees were successfully separated by this model of roasting-level discrimination. 'Naphthalene, 1,2,3,4-tetrahydro-1,6,8-trimethyl-', '1,1,5-trimethyl-1,2-dihydronaphthalene', '-Xylene', 'alpha.-methyl-.alpha.-[4-methyl-3-pentenyl]oxiranemethanol', 'hydrazinecarboxylic acid, phenylmethyl ester', and '3-buten-2-one, 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-' might be key characteristic markers for the roasting process of Wuyi rock tea.
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http://dx.doi.org/10.1039/d0ra09703aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696517PMC
March 2021
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