Publications by authors named "Yun Li"

2,575 Publications

  • Page 1 of 1

A comprehensive comparison on cell-type composition inference for spatial transcriptomics data.

Brief Bioinform 2022 Jun 27. Epub 2022 Jun 27.

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Spatial transcriptomics (ST) technologies allow researchers to examine transcriptional profiles along with maintained positional information. Such spatially resolved transcriptional characterization of intact tissue samples provides an integrated view of gene expression in its natural spatial and functional context. However, high-throughput sequencing-based ST technologies cannot yet reach single cell resolution. Thus, similar to bulk RNA-seq data, gene expression data at ST spot-level reflect transcriptional profiles of multiple cells and entail the inference of cell-type composition within each ST spot for valid and powerful subsequent analyses. Realizing the critical importance of cell-type decomposition, multiple groups have developed ST deconvolution methods. The aim of this work is to review state-of-the-art methods for ST deconvolution, comparing their strengths and weaknesses. In particular, we construct ST spots from single-cell level ST data to assess the performance of 10 methods, with either ideal reference or non-ideal reference. Furthermore, we examine the performance of these methods on spot- and bead-level ST data by comparing estimated cell-type proportions to carefully matched single-cell ST data. In comparing the performance on various tissues and technological platforms, we concluded that RCTD and stereoscope achieve more robust and accurate inferences.
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http://dx.doi.org/10.1093/bib/bbac245DOI Listing
June 2022

Environmentally relevant concentrations of tris (1,3-dichloro-2-propyl) phosphate induce growth inhibition and oxidative stress in silver carp (Hypophthalmichthys molitrix) larvae.

Ecotoxicol Environ Saf 2022 Jun 21;241:113798. Epub 2022 Jun 21.

Fisheries and Aquaculture Biotechnology Laboratory, College of Fisheries, Southwest University, Chongqing 400715, China. Electronic address:

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), widely applied as flame retardant into a variety of products, can be physically leached out to the aquatic environment. Measurable values of TDCIPP have been found in the environment and within biota. Many toxicological assessments have shown that TDCIPP could cause developmental toxicity and oxidative stress in fish. In this study, we focused on the effects of TDCIPP on the growth and oxidative stress of an important commercial fish species in China, silver carp (Hypophthalmichthys molitrix). Fish larvae was exposed to environmentally relevant concentrations (0.05, 0.5, 5 and 50 μg/L) of TDCIPP for 7, 14 and 28 days. Simultaneously, the transcription levels of genes associated with the growth hormone/insulin-like growth factor (GH/IGF) axis and the antioxidative enzymes were examined. The body length and body mass of silver carp larvae decreased significantly only under exposure to 5 and 50 μg/L of TDCIPP at 14 days compared with the control group, while differences on those paraments were observed at 0.05, 0.5, 5 and 50 μg/L when larvae were exposed for 28 days. The observation evidenced the time- and dose- dependent growth inhibitions caused by TDCIPP on silver carp larvae. Exposure to TDCIPP also decreased the contents of GH and IGF1 in fish attended by significant down-regulation of gh and igf1. Moreover, TDCIPP up-regulated the expression of cat, sod1 and gstt followed by an increase of the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) and glutathione (GSH), but the activities of glutathione peroxidase (GPX) were decreased. These results suggested that growth inhibition and oxidative stress co-occurred in silver carp larvae after exposure to environmentally relevant concentrations of TDCIPP accompanied by the abnormal expression of genes which associated with the GH/IGF axis and antioxidative enzymes.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113798DOI Listing
June 2022

Antifibrotic Mechanism of Piceatannol in Bleomycin-Induced Pulmonary Fibrosis in Mice.

Front Pharmacol 2022 7;13:771031. Epub 2022 Jun 7.

Xingzhi College, Zhejiang Normal University, Lanxi, China.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by myofibroblast accumulation and extracellular matrix deposition, which lead to irreversible damage of the lung's architecture and the formation of fibrotic lesions. IPF is also a sequela in serious patients with the coronavirus disease 2019 (COVID-19). The molecular mechanisms under pulmonary fibrosis remain unclear, and there is no satisfactory treatment currently available. Piceatannol (PIC) is a naturally occurring resveratrol analog found in a variety of dietary sources such as grapes, passion fruit, and white tea. It has been reported to inhibit liver fibroblast growth and exhibited various antitumor activities, although its role in pulmonary fibrosis has not been established yet. In the present study, we evaluated the anti-fibrotic role of PIC in bleomycin (BLM)-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with PIC, and fibrotic changes were measured by hematoxylin-eosin (H&E) staining and hydroxyproline assay. Luciferase assay, Western blot assay, histological analysis, and immunofluorescence staining were used to evaluate the effect of PIC on fibroblast activation and autophagy in mouse embryonic fibroblast cells (NIH-3T3) and human lung fibroblast cells (HFL1). The anti-fibrotic mechanisms of PIC were either confirmed . Our results showed that PIC significantly alleviated the bleomycin-induced collagen deposition and myofibroblast accumulation. and studies indicated that PIC plays a role in activating autophagy in the process of anti-fibroblast activation. Further mechanism studies demonstrated that PIC can promote autophagy inhibiting the TGF-β1-Smad3/ERK/P38 signaling pathway, which leads to a decreased number of activated myofibroblasts. Our study demonstrated for the first time that PIC possesses the protective effects against bleomycin-induced pulmonary fibrosis due to the direct pulmonary protective effects which enhance the effect of autophagy and and finally leads to the decreased number of activated myofibroblasts. PIC may serve as a candidate compound for pulmonary fibrosis therapy and attenuates the sequelae of SARS-COV-2 pulmonary fibrosis.
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http://dx.doi.org/10.3389/fphar.2022.771031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209743PMC
June 2022

A novel c.68delC variant is associated with progressive hearing loss in Chinese population and literature review.

Laryngoscope Investig Otolaryngol 2022 Jun 27;7(3):870-876. Epub 2022 May 27.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.

Objective: The aim of this study was to identify genetic etiology in two unrelated Chinese probands with progressive sensorineural hearing loss.

Methods: Two unrelated Chinese families were recruited. Genetic etiology was identified by targeted next-generation sequencing (NGS) and verified by Sanger sequencing. Hearing evaluations included pure tone audiometry, auditory brainstem response to clicks, and otoscopic examination. Medical history and computerized tomography scan of temporal bone were also collected. In addition, linear regression was used to summarize all of the reported cases and estimate the progression of hearing loss.

Results: A 28-year-old man with variant c.68delC had progressive, moderately severe hearing loss and a suspicious history of renal impairment. His hearing result was 63.75 dB HL. The other proband was the youngest patient with MPZL2-related hearing loss reported so far in the literature (genotype: c.220C>T homozygote). Her hearing result by click-ABR was 25 dB nHL at 3 months of age, and deteriorated to 40 dB nHL at 15 months. Behavioral audiometry identified a hearing loss of 26.25 dB HL. In summarizing all of the reported cases, using linear regression, MPZL2-related hearing loss may deteriorate by 0.59 dB HL per year, and different MPZL2 variants may lead to different rates of progression.

Conclusion: In this study, we first identified two unrelated patients with -related hearing loss in Chinese population, and a novel variant c.68delC. Our results expanded the mutation spectrum of deafness genes. Further studies are required to clarify the genotype-phenotype correlation and the progression of -related hearing loss.
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http://dx.doi.org/10.1002/lio2.829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194966PMC
June 2022

Proteomic Changes to the Updated Discovery of Engineered Insulin and Its Analogs: Pros and Cons.

Curr Issues Mol Biol 2022 Feb 11;44(2):867-888. Epub 2022 Feb 11.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University, Chengdu 611130, China.

The destruction of β-cells of the pancreas leads to either insulin shortage or the complete absence of insulin, which in turn causes diabetes Mellitus. For treating diabetes, many trials have been conducted since the 19th century until now. In ancient times, insulin from an animal's extract was taken to treat human beings. However, this resulted in some serious allergic reactions. Therefore, scientists and researchers have tried their best to find alternative ways for managing diabetes with progressive advancements in biotechnology. However, a lot of research trials have been conducted, and they discovered more progressed strategies and approaches to treat type I and II diabetes with satisfaction. Still, investigators are finding more appropriate ways to treat diabetes accurately. They formulated insulin analogs that mimic the naturally produced human insulin through recombinant DNA technology and devised many methods for appropriate delivery of insulin. This review will address the following questions: What is insulin preparation? How were these devised and what are the impacts (both positive and negative) of such insulin analogs against TIDM (type-I diabetes mellitus) and TIIDM (type-II diabetes mellitus)? This review article will also demonstrate approaches for the delivery of insulin analogs into the human body and some future directions for further improvement of insulin treatment.
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http://dx.doi.org/10.3390/cimb44020059DOI Listing
February 2022

Effect of PARP Inhibitor Combined with Bevacizumab on Platinum-Resistant Recurrent Ovarian Epithelial Carcinoma.

Comput Math Methods Med 2022 10;2022:4600145. Epub 2022 Jun 10.

Department of Gynecology, Hanzhong Central Hospital, No. 22 Kangfu Road, Hanzhong, Shaanxi 723000, China.

Objective: This study was aimed at investigating the efficacy of PARP inhibitor combined with bevacizumab in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma.

Methods: A total of 84 patients with platinum-resistant recurrent ovarian epithelial carcinoma treated in our hospital from May 2017 to June 2018 were selected as the research objects. The patients were divided into observation group ( = 42) and control group ( = 42) according to random number table method. The observation group was treated with olaparib combined with bevacizumab, while the control group was treated with albumin-bound paclitaxel combined with bevacizumab, and the clinical efficacy of the two groups was observed. The levels of serum carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and epididymal protein 4 (HE4) were determined. The levels of miRNA124, mirNA-21, and miRNA-203 in the two groups were detected. The incidence of adverse reactions was compared between the two groups. The quality of life of the two groups was assessed using FACT-G scale. The drug safety of the two groups was observed. All patients were followed up for 3 years, and the survival time of the two groups was recorded. The Kaplan-Meier method was used to analyze the survival of the two groups.

Results: The overall response rate (ORR) (69.05%) and disease control rate (DCR) (88.10%) of the observation group were higher than those of the control group (40.48% and 66.67%), and the differences were statistically significant (both < 0.05). After treatment, the levels of serum CA125, CA199, HE4, miRNA124, miRNA-21, and miRNA-203 and the improvement degree of quality of life score in the observation group were greater than those in the control group, with statistical significances (all < 0.05).The 1-year, 2-year, and 3-year survival rates of the observation group (97.62%, 88.10%, and 80.95%) were higher than those of the control group (71.43%, 57.14%, and 47.62%), with statistical significances (all > 0.05).

Conclusion: PARP inhibitor combined with bevacizumab had good effect in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma and can effectively improve the survival time and quality of life of patients.
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http://dx.doi.org/10.1155/2022/4600145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205723PMC
June 2022

Effect of automatic emotional processing on response inhibition among heroin abstainers.

Psych J 2022 Jun 14. Epub 2022 Jun 14.

Key Laboratory of Behavioral and Mental Health of Gansu Province, Department of Psychology, Northwest Normal University, Lanzhou, People's Republic of China.

Previous studies have explored effects of the conscious processing of emotional information on the interaction between emotion and executive control. However, the conscious processing of emotional information introduces "defensive responses," which might limit the emotional effect. To avoid the limitations, this study aimed to explore the effect of automatic emotional processing on response inhibition among heroin abstainers. Individuals experiencing heroin withdrawal symptoms are not entirely exempt from the influence of drugs, and it is challenging to find heroin addicts in practice. Therefore, similar to previous studies, we recruited heroin abstainers in this study. In Experiment 1, for the heroin abstainers group, 30 participants meeting the inclusion criteria were recruited from a compulsory isolated detoxification center, whereas 30 age- and education-matched participants were recruited from the community as the control group. These participants completed the Go/No-Go task by supraliminal emotional priming. In Experiment 2, the heroin abstainers group comprised 33 eligible participants and control group comprised 33 eligible participants. These participants completed the Go/No-Go task by subliminal emotional priming. We compared the participants' rates of commission errors in the Go/No-Go tasks. The rate of commission errors was lowest upon the activation of positive emotion. Moreover, under subliminal emotional priming, the rate of commission errors for the heroin abstainers group was significantly lower than that for the control group. However, regarding supraliminal emotional priming, there was no significant difference between the rates of commission errors for the two groups. These results suggest automatic positive emotional processing can enhance response inhibition among heroin abstainers. Moreover, under subliminal emotional priming, heroin abstainers had more enhanced response inhibition than the control groups. This study plays a significant role in understanding the effect of automatic emotional processing on response inhibition among drug addicts. This study also provides a theoretical basis for ensuring enhanced response inhibition among drug addicts.
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http://dx.doi.org/10.1002/pchj.574DOI Listing
June 2022

Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice.

J Neuroinflammation 2022 Jun 11;19(1):141. Epub 2022 Jun 11.

Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Background: Neuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization.

Methods: We evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing.

Results: ITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1β, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1β, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1/CD86) and enhancing the anti-inflammatory M2 activation (Iba1/CD206) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment.

Conclusions: rTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke.
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http://dx.doi.org/10.1186/s12974-022-02501-2DOI Listing
June 2022

[Effect of HumicAcid-Heavy Metals on the Nitrogen Removal Performance of ANAMMOX Bacteria and Its Kinetic Analysis].

Huan Jing Ke Xue 2022 Jun;43(6):3221-3229

College of Architecture and Civil Engineering, Beijing University of Technology, Beijing 100124, China.

The effects of two typical heavy metal ions[Cu(Ⅱ) and Ni(Ⅱ)] and humic acid on ANAMMOX nitrogen removal (SAA) were studied through batch experiments, and the kinetic model was analyzed. At the same time, the effects of humic acid-heavy metal on ANAMMOX nitrogen removal were discussed. The results showed that ANAMMOX was promoted when [Cu(Ⅱ)] and [Ni(Ⅱ)] were 3 mg·L, and SAA was increased by 8.64% and 7.78%, respectively; ANAMMOX was inhibited when the [Cu(Ⅱ)] and [Ni(Ⅱ)] were 20 mg·L and 5 mg·L, respectively, and the inhibition effect was more significant with the increase in heavy metal ion concentration. The index fitting showed that the IC50 of Cu(Ⅱ) and Ni(Ⅱ) on ANAMMOX were 29.67 mg·L and 28.75 mg·L, respectively. SAA was increased by 7.37% when the (humic acid) was 1 mg·L, and the inhibition rate reached 36.80% when the humic acid concentration was 40 mg·L. The linear fitting showed that the IC50 of humic acid on ANAMMOX was 58.36 mg·L. The modified Michaelis-Menten model could better describe the inhibitory kinetic behavior of heavy metals and humic acid on ANAMMOX. The model fitting showed that the complete inhibition concentrations () of Cu(Ⅱ), Ni(Ⅱ), and humic acid on ANAMMOX were 49.59, 74.46, and 84.27 mg·L, respectively. An appropriate amount of humic acid was beneficial to improve the inhibition of heavy metals on ANAMMOX bacteria activity, and excessive humic acid would cause inhibition on ANAMMOX bacteria again.
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http://dx.doi.org/10.13227/j.hjkx.202110114DOI Listing
June 2022

Clinical and cVEMP Evaluation Predict Short-Term Residual Dizziness After Successful Repositioning in Benign Paroxysmal Positional Vertigo.

Front Med (Lausanne) 2022 24;9:881307. Epub 2022 May 24.

Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: Residual dizziness (RD) is a frequent symptom with unknown pathogenesis, often complained about by the patients with benign paroxysmal positional vertigo (BPPV), even after a successful canalith repositioning procedure (CRP). This study aims to quantitatively evaluate the short-term RD severity and its risk factors in patients with BPPV after successful CRPs.

Methods: In total two hundred and twenty patients with BPPV after successful CRPs (W0) were prospectively followed up for 1 week (W1). Besides demographics and serial neuropsychological assessments (including dizziness handicap inventory-DHI, etc.), patients also received cervical/ocular vestibular evoked myogenic potential (c/oVEMP) evaluation. RD was defined as patients with dizziness or imbalance, dizziness visual analog scale (VAS) >1, and without positional vertigo or nystagmus at W1. Demographic, clinical, and VEMPs differences were compared among the three groups: patients with minor (dizziness VAS 1-3) and moderate-to-severe RD (dizziness VAS > 3) and without RD.

Results: The total frequency of RD at W1 was 49.1% ( = 108), with 32.3% ( = 71) minor, and 16.8% ( = 37) moderate-to-severe RD. Logistic regression analyses revealed that RD was closely associated with DHI status (OR = 2.101, = 0.008) at W0, this effect was not present for minor RD. In addition to DHI score > 30 (OR = 4.898, < 0.001) at W0, bilateral cVEMP absence (OR = 4.099, = 0.005) was also an independent influential factor of moderate-to-severe RD.

Conclusion: Our study highlights the importance of RD quantified evaluation. DHI score >30 and bilateral cVEMP absence could increase the risk of short-term moderate-to-severe RD.
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http://dx.doi.org/10.3389/fmed.2022.881307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170995PMC
May 2022

SnapHiC2: A computationally efficient loop caller for single cell Hi-C data.

Comput Struct Biotechnol J 2022 1;20:2778-2783. Epub 2022 Jun 1.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Single cell Hi-C (scHi-C) technologies enable the study of chromatin spatial organization directly from complex tissues at single cell resolution. However, the identification of chromatin loops from single cells is challenging, largely due to the extremely sparse data. Our recently developed SnapHiC pipeline provides the first tool to map chromatin loops from scHi-C data, but it is computationally intensive. Here we introduce SnapHiC2, which adapts a sliding window approximation when imputing missing contacts in each single cell and reduces both memory usage and computational time by 70%. SnapHiC2 can identify 5 Kb resolution chromatin loops with high sensitivity and accuracy and help to suggest target genes for GWAS variants in a cell-type-specific manner. SnapHiC2 is freely available at: https://github.com/HuMingLab/SnapHiC/releases/tag/v0.2.2.
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http://dx.doi.org/10.1016/j.csbj.2022.05.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168059PMC
June 2022

In-depth profiling, nontargeted metabolomic and selective ion monitoring of eight chemical markers for simultaneous identification of different part of Eucommia ulmoides in 12 commercial products by UPLC/QDa.

Food Chem 2022 Nov 30;393:133346. Epub 2022 May 30.

Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China. Electronic address:

Despite Eucommia ulmoides to be served as a crucial source for food additives and healthcare products, unclarity of the metabolomic differences among four different plant parts (bark, leaf, flower, seed) seriously restricts the comprehensive quality control of the herb and its related commercial products. In this study, a strategy integrating in-depth profiling, nontargeted metabolomics, and selected detection was established and exemplarily applied to authenticate E. ulmoides related products. UPLC/Q-TOF Fast DDA approach was utilized for in-depth profiling among four parts to characterize 222 compounds. In addition, 38 batches of different parts of E. ulmoides were compared by metabolomics method, and multi-step chemometrics analysis to unveil 25 chemical markers. Finally, an UPLC/QDa-SIM method was established based 8 most important diagnosis components to identify 12 commercial products. This study provides a novel and comprehensive strategy for the quality assessment of foods and dietary supplements.
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http://dx.doi.org/10.1016/j.foodchem.2022.133346DOI Listing
November 2022

Photoredox/copper cocatalyzed domino cyclization of oxime esters with TMSCN: access to antifungal active tetrasubstituted pyrazines.

Chem Commun (Camb) 2022 Jun 23;58(51):7200-7203. Epub 2022 Jun 23.

Jiangsu Key Laboratory of Pesticide Science and Department of Chemistry, College of Sciences, Nanjing Agricultural University, Nanjing 210095, P. R. China.

A photoredox/copper cocatalyzed domino cyclization of oxime esters with TMSCN has been developed. A range of structurally novel tetrasubstituted pyrazines have been obtained. This method features high bond-forming efficiency, high step economy, broad substrate scope, and gram-scale synthesis. Moreover, preliminary bioactivity evaluation of pyrazine products shows their promising antifungal activities.
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http://dx.doi.org/10.1039/d2cc02480bDOI Listing
June 2022

Lymphovascular invasion: A non-sized T descriptor for stage IA non-small cell lung cancer.

Thorac Cancer 2022 Jun 7. Epub 2022 Jun 7.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, People's Republic of China.

Background: Lymphovascular invasion (LVI) has not been included in the tumor-node-metastasis (TNM) staging manual of non-small-cell lung cancer (NSCLC). We aimed to investigate the predictive value of LVI on stage IA NSCLC and proposed a method of incorporating LVI into the T category based on the latest TNM staging manual.

Methods: The least absolute shrinkage and selection operator (LASSO)-penalized Cox multivariable regression model was performed to identify prognostic factors. The Kaplan-Meier method was used to compare overall survival (OS) and disease-free survival (DFS) between groups. Propensity score matching (PSM) was used to minimize bias.

Results: A total of 1452 eligible stage I NSCLC cases (stage IA without LVI, 1022 cases; stage IA with LVI, 120 cases; stage IB, 310 cases) were included. LASSO-penalized multivariable Cox analysis revealed that LVI was an independent prognostic factor for both OS and DFS. Survival analysis demonstrated that the survivals of stage IA NSCLCs without LVI were better than those of stage IA with LVI and stage IB NSCLCs. In the matched cohort, the survivals of stage IA NSCLCs with LVI were comparable to those of stage IB NSCLCs.

Conclusions: Stage IA NSCLCs with LVI and stage IB NSCLCs had similar survivals, and we proposed that LVI might be a non-sized T descriptor that upstaged stage IA diseases to stage IB.
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http://dx.doi.org/10.1111/1759-7714.14530DOI Listing
June 2022

Aberrant neural activity in prefrontal pyramidal neurons lacking TDP-43 precedes neuron loss.

Prog Neurobiol 2022 Aug 4;215:102297. Epub 2022 Jun 4.

Department of Zoology and Physiology, University of Wyoming, 1000 E University Avenue, Laramie, WY 82071, USA. Electronic address:

Mislocalization of TAR DNA binding protein 43 kDa (TARDBP, or TDP-43) is a principal pathological hallmark identified in cases of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As an RNA binding protein, TDP-43 serves in the nuclear compartment to repress non-conserved cryptic exons to ensure the normal transcriptome. Multiple lines of evidence from animal models and human studies support the view that loss of TDP-43 leads to neuron loss, independent of its cytosolic aggregation. However, the underlying pathogenic pathways driven by the loss-of-function mechanism are still poorly defined. We employed a genetic approach to determine the impact of TDP-43 loss in pyramidal neurons of the prefrontal cortex (PFC). Using a custom-built miniscope imaging system, we performed repetitive in vivo calcium imaging from freely behaving mice for up to 7 months. By comparing calcium activity in PFC pyramidal neurons between TDP-43 depleted and TDP-43 intact mice, we demonstrated remarkably increased numbers of pyramidal neurons exhibiting hyperactive calcium activity after short-term TDP-43 depletion, followed by rapid activity declines prior to neuron loss. Our results suggest aberrant neural activity driven by loss of TDP-43 as the pathogenic pathway at early stage in ALS and FTD.
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http://dx.doi.org/10.1016/j.pneurobio.2022.102297DOI Listing
August 2022

Association of protein function-altering variants with cardiometabolic traits: the strong heart study.

Sci Rep 2022 Jun 4;12(1):9317. Epub 2022 Jun 4.

Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.

Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencing of American Indians. We tested the association of each SNV/indel with 35 cardiometabolic traits. Among 1206 variants (average minor allele count = 20, range of 1 to 1064), ~ 43% were not present in publicly available repositories. We identified seven SNV-trait significant associations including a missense SNV at ABCA10 (rs779392624, p = 8 × 10) associated with fasting triglycerides, which gene product is involved in macrophage lipid homeostasis. Among non-diabetic individuals, missense SNVs at four genes were associated with fasting insulin adjusted for BMI (PHIL, chr6:79,650,711, p = 2.1 × 10; TRPM3, rs760461668, p = 5 × 10; SPTY2D1, rs756851199, p = 1.6 × 10; and TSPO, rs566547284, p = 2.4 × 10). PHIL encoded protein is involved in pancreatic β-cell proliferation and survival, and TRPM3 protein mediates calcium signaling in pancreatic β-cells in response to glucose. A genetic risk score combining increasing insulin risk alleles of these four genes was associated with 53% (95% confidence interval 1.09, 2.15) increased odds of incident diabetes and 83% (95% confidence interval 1.35, 2.48) increased odds of impaired fasting glucose at follow-up. Our study uncovered novel gene-trait associations through the study of protein-coding variants and demonstrates the advantages of association screenings targeting diverse and high-risk populations to study variants absent in publicly available repositories.
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http://dx.doi.org/10.1038/s41598-022-12866-2DOI Listing
June 2022

Synergism of eravacycline combined with other antimicrobial agents against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii.

J Glob Antimicrob Resist 2022 May 31;30:56-59. Epub 2022 May 31.

Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China. Electronic address:

Objectives: This study aimed to investigate the synergistic activity of eravacycline combined with other antimicrobial agents against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii collected from China.

Methods: Sixty carbapenem-resistant strains, including 20 Escherichia coli, 20 Klebsiella pneumoniae, and 20 Acinetobacter baumannii were investigated for the synergy analysis. Imipenem, ceftazidime, cefoperazone-sulbactam, ciprofloxacin, amikacin, and polymyxin B were selected to investigate their efficacy in combination with eravacycline against 60 carbapenem-resistant strains. Minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution method. The efficacy of eravacycline in combination with these agents was determined by the chequerboard method.

Results: Antimicrobial susceptibility testing revealed that polymyxin B was most effective against all carbapenem-resistant strains, with resistance rates between 0% and 15%. Eravacycline showed potent activity against E. coli with an 85% susceptibility rate, and may also have activity against K. pneumoniae and A. baumannii with low MIC values. The chequerboard method showed that eravacycline-polymyxin B was the most effective combination against E. coli and K. pneumoniae, with more than 30% synergy. The most active combination against A. baumannii was eravacycline-ceftazidime and eravacycline-imipenem, which showed synergy in more than 50% of isolates.

Conclusion: Eravacycline combined with β-lactams or polymyxin B can lead to synergistic effects against clinically common carbapenem-resistant Gram-negative bacteria. The synergistic effects of eravacycline-based combinations varied in different species. A combination of eravacycline and polymyxin B may be considered for the treatment of carbapenem-resistant E. coli and K. pneumoniae; eravacycline in combination with ceftazidime or a carbapenem antimicrobial may be considered for the treatment of carbapenem-resistant A. baumannii.
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http://dx.doi.org/10.1016/j.jgar.2022.05.020DOI Listing
May 2022

Frailty in rodents: Models, underlying mechanisms, and management.

Ageing Res Rev 2022 Jun 2;79:101659. Epub 2022 Jun 2.

Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, China. Electronic address:

Frailty is a clinical geriatric syndrome characterized by decreased multisystem function and increased vulnerability to adverse outcomes. Although numerous studies have been conducted on frailty, the underlying mechanisms and management strategies remain unclear. As rodents share homology with humans, they are used extensively as animal models to study human diseases. Rodent frailty models can be classified broadly into the genetic modification and non-genetic modification models, the latter of which include frailty assessment models (based on the Fried frailty phenotype and frailty index methods) and induced frailty models. Such models were developed for use in investigating frailty-related physiological changes at the gene, cellular, molecular, and system levels, including the organ system level. Furthermore, exercise, diet, and medication interventions, in addition to their combinations, could improve frailty status in rodents. Rodent frailty models provide novel and effective tools for frailty research. In the present paper, we review research progress in rodent frailty models, mechanisms, and management, which could facilitate and guide further clinical research on frailty in older adults.
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http://dx.doi.org/10.1016/j.arr.2022.101659DOI Listing
June 2022

Response to Letter to the Editor, "Sarcopenic Obesity: An Emerging Public Health Problem, But an Answer Appears to Be Available".

Aging Dis 2022 Jun 1;13(3):637-638. Epub 2022 Jun 1.

Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Research Center for Geriatric Medicine, Beijing 100053, China.

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http://dx.doi.org/10.14336/AD.2021.1120-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116924PMC
June 2022

Management of Malnutrition Based on Multidisciplinary Team Decision-Making in Chinese Older Adults (3M Study): A Prospective, Multicenter, Randomized, Controlled Study Protocol.

Front Nutr 2022 9;9:851590. Epub 2022 May 9.

Department of Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China.

Background: In hospital settings, malnutrition affects 30-50% of aged inpatients and is related to a higher risk of hospital complications and death. This study aims to demonstrate the effectiveness of a tailored optimum nutritional therapy in malnourished, elderly inpatients based on multidisciplinary team recommendations in hopes of decreasing the incidence of deleterious clinical outcomes.

Methods And Design: This trial will be a multicenter, open-label, randomized control trial conducted in the geriatric wards of at least five hospitals in five different regions. We aim to include 500 inpatients over the age of 60 with or at risk of malnutrition based on a Mini Nutritional Assessment Short-Form (MNA-SF) score of ≤ 11 points and the Global Leadership Initiative on Malnutrition with an expected length of stay of ≥ 7 days. Eligible inpatients will be randomized into a 1:1 ratio, with one receiving a multidisciplinary team intervention and the other receiving standard medical treatment or care alone. A structured comprehensive assessment of anthropometry, nutritional status, cognition, mood, functional performance, and quality of life will be conducted twice. These assessments will take place on the day of group allocation and 1 year after discharge, and a structured screening assessment for elderly malnutrition will be conducted at 3 and 6 months after discharge using the MNA-SF. The primary outcome will be nutritional status based on changes in MNA-SF scores at 3, 6 months, and 1 year. The secondary outcome will be changes in cognition, mood, functional status, length of hospital stay, and all-cause mortality 1 year after discharge.

Discussion: Guided by the concept of interdisciplinary cooperation, this study will establish a multidisciplinary nutrition support team that will develop an innovative intervention strategy that integrates nutritional screenings, evaluations, education, consultation, support, and monitoring. Moreover, nutritional intervention and dietary fortification will be provided to hospitalized elderly patients with or at risk of malnutrition. The nutrition support team will formulate a clinical map for malnutrition in elderly patients with standardized diagnosis and treatment for malnutrition in this population.

Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2200055331].
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http://dx.doi.org/10.3389/fnut.2022.851590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150743PMC
May 2022

Depleting receptor tyrosine kinases EGFR and HER2 overcomes resistance to EGFR inhibitors in colorectal cancer.

J Exp Clin Cancer Res 2022 Jun 2;41(1):184. Epub 2022 Jun 2.

Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.

Background: Epidermal growth factor receptor (EGFR) inhibitors, including cetuximab and panitumumab, are valuable therapeutics for colorectal cancer (CRC), but resistance to these inhibitors is common. The reason for such resistance is not well understood, which hampers development of better therapeutic strategies. Although activating mutations in KRAS, BRAF and PIK3CA are considered major drivers of CRC resistance to EGFR inhibitors, therapeutic targeting of these drug resistance drivers has not produced substantial clinical benefit.

Methods: We exploited cell lines and mouse tumor models (cell line xenografts and patient derived xenografts) for experiments of genetic and pharmacologic depletion of EGFR and/or its family member HER2, including EGFR mutants, inhibition of EGFR ligand shedding, and biochemical analysis of signaling proteins, to delineate the mechanism of CRC resistance to EGFR inhibitors and to assess the therapeutic activity of PEPD, which is a recombinant human protein that induces the degradation of both EGFR and HER2.

Results: The sensitivity of CRC cells to cetuximab and panitumumab correlates with the ability of these drugs to induce EGFR downregulation. PEPD strongly inhibits oncogenic signaling and growth of CRC cells by causing profound depletion of EGFR and HER2, regardless of activating mutations of KRAS, BRAF and PIK3CA. siRNA knockdown of EGFR or HER2 also inhibits CRC cells resistant to EGFR inhibitors. Tumors harboring mutated KRAS, BRAF and/or PIK3CA also overexpress EGFR ligands, further suggesting that EGFR signaling remains important to the tumors. While excessive tumor-generated high-affinity EGFR ligands block target engagement by PEPD, aderbasib, an inhibitor of ADAM10 and ADAM17, enables PEPD to exert strong antitumor activity by inhibiting ligand shedding. Moreover, adding fluorouracil, which is commonly used in CRC treatment, to the combination of PEPD and aderbasib further enhances tumor inhibition.

Conclusions: Our study shows that CRC resistance to EGFR inhibitors results primarily from the inability of the inhibitors to downregulate their target and that a PEPD-based combination treatment overcomes the resistance.
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http://dx.doi.org/10.1186/s13046-022-02389-zDOI Listing
June 2022

Recent insights into greywater treatment: a comprehensive review on characteristics, treatment technologies, and pollutant removal mechanisms.

Environ Sci Pollut Res Int 2022 Jun 1. Epub 2022 Jun 1.

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

With the rapid socio-economic and industrial development, the problem of water shortage is becoming increasingly serious. Seeking alternative water sources to reduce the need for freshwater resources is an increasing concern. Household greywater production is high and accounts for about 50-80% of domestic wastewater. In recent years, the in situ treatment and reuse of greywater have received widespread attention. Treated greywater can be used for non-potable purposes such as toilet flushing and irrigation, which can greatly reduce the pressure of freshwater resource shortage. This paper reviews the sources and characteristics of greywater and analyzes its quantity and quality. In addition, this paper outlines and summarizes various greywater treatment technologies commonly used, including physical, biological, and chemical treatment technologies, as well as combination technologies. Understanding the mechanisms of contaminant removal is essential for effective greywater treatment. While discussing different treatment technologies, we focus on the removal mechanisms of pollutants from greywater, including organics, nutrients, surfactants, and emerging contaminants. Finally, future perspectives on greywater management and reuse are presented. Through a comprehensive review, we expect that this review will help the reader to better understand the characteristics of greywater and to more rationally select the appropriate treatment technology based on the removal mechanism of pollutants.
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http://dx.doi.org/10.1007/s11356-022-21070-8DOI Listing
June 2022

Effects of Different Draw Solutions on Biogas Slurry Concentration in Forward Osmosis Membrane: Performance and Membrane Fouling.

Membranes (Basel) 2022 Apr 28;12(5). Epub 2022 Apr 28.

Institute of Agricultural Resources and Environment, Guizhou Academy of Agricultural Sciences, Guiyang 550006, China.

Biogas slurry poses a severe challenge to the sustainable management of livestock farms. The technology of the forward osmosis (FO) membrane has a good application prospect in the field of biogas slurry concentration. Further research is needed to verify the effects of different draw solutions on FO membranes in biogas slurry treatment and the related membrane fouling characteristics. In this study, three different draw solutions were selected to evaluate the performance of FO membranes for biogas slurry concentration. Membrane fouling was investigated by characterization after FO membrane treatment to identify fouling contaminants. The result showed that FO membrane treatment can realize the concentration of biogas slurry and MgCl as the draw solution has the best effect on the concentration of biogas slurry. The different draw solutions all contributed to the efficient retention of most organics and TP while each treatment was ineffective at retaining nitrogen. The cake layer that appeared after the biogas slurry was concentrated covered the surface of the FO membrane. Some functional groups were detected on the surface after membrane fouling, such as C-O and C=C. Moreover, the C element accounts for 57% of the main components of the cake layer after the membrane fouling. Membrane fouling is caused by both organic fouling and inorganic fouling, of which organic fouling is the main reason. This study provides a technical reference for the high-value utilization of biogas slurry.
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http://dx.doi.org/10.3390/membranes12050476DOI Listing
April 2022

Rethink, Revisit, Revise: A Spiral Reinforced Self-Revised Network for Zero-Shot Learning.

IEEE Trans Neural Netw Learn Syst 2022 May 27;PP. Epub 2022 May 27.

Current approaches to zero-shot learning (ZSL) struggle to learn generalizable semantic knowledge capable of capturing complex correlations. Inspired by Spiral Curriculum, which enhances learning processes by revisiting knowledge, we propose a form of spiral learning that revisits visual representations based on a sequence of attribute groups (e.g., a combined group of color and shape). Spiral learning aims to learn generalized local correlations, enabling models to gradually enhance global learning and, thus, understand complex correlations. Our implementation is based on a two-stage reinforced self-revised (RSR) framework: preview and review. RSR first previews visual information to construct diverse attribute groups in a weakly supervised manner. Then, it spirally learns refined localities based on attribute groups and uses localities to revise global semantic correlations. Our framework outperforms state-of-the-art algorithms on four benchmark datasets in both zero-shot and generalized zero-shot settings, which demonstrates the effectiveness of spiral learning in learning generalizable and complex correlations. We also conduct extensive analysis to show that attribute groups and reinforced decision processes can capture complementary semantic information to improve predictions and aid explainability.
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http://dx.doi.org/10.1109/TNNLS.2022.3176282DOI Listing
May 2022

The Association Between the Frequency of Annual Health Checks Participation and the Control of Cardiovascular Risk Factors.

Front Cardiovasc Med 2022 10;9:860503. Epub 2022 May 10.

Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: General health checks can help in controlling cardiovascular risk factors. However, few studies have investigated whether regular participation in annual health checks could further improve the control of cardiovascular risk factors compared with intermittent participation. Therefore, our study aimed to explore the association between the frequency of annual health check participation and the control of cardiovascular risk factors.

Methods: Residents aged ≥ 65 years or having chronic diseases (hypertension or diabetes) from 37 communities of Guangzhou, Guangdong, who participated in the Basic Public Health Service project between January 2015 and December 2019, were enrolled and divided into 3 groups ("Sometimes," "Usually," and "Always") according to their frequencies of annual health check participation. Multivariable linear regression models were performed to assess the association between the frequency of annual health check participation and the control of cardiovascular risk factors. A subgroup analysis stratified by gender was also conducted.

Results: In total, 9,102 participants were finally included. Significant differences were identified between groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and serum creatinine. After fully adjusting for confounding factors, residents who always participated in the annual health check tended to have lower SBP (β = -4.36, 95% : -5.46; -3.26, < 0.001), fasting glucose (β = -0.27, 95% : -0.38; -0.15, < 0.001), and total cholesterol (β = -0.19, 95% CI: -0.26; -0.13, < 0.001), compared with those who attended sometimes. Furthermore, gender did not alter these associations.

Conclusion: A higher frequency of annual health check participation was associated with lower SBP, fasting glucose, and total cholesterol.
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http://dx.doi.org/10.3389/fcvm.2022.860503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127134PMC
May 2022

CrisprVi: a software for visualizing and analyzing CRISPR sequences of prokaryotes.

BMC Bioinformatics 2022 May 11;23(Suppl 3):172. Epub 2022 May 11.

Jiangsu Key Laboratory of Zoonosis, Yangzhou, People's Republic of China.

Background: Clustered regularly interspaced short palindromic repeats (CRISPR) and their spacers are important components of prokaryotic CRISPR-Cas systems. In order to analyze the CRISPR loci of multiple genomes more intuitively and comparatively, here we propose a visualization analysis tool named CrisprVi.

Results: CrisprVi is a Python package consisting of a graphic user interface (GUI) for visualization, a module for commands parsing and data transmission, local SQLite and BLAST databases for data storage and a functions layer for data processing. CrisprVi can not only visually present information of CRISPR direct repeats (DRs) and spacers, such as their orders on the genome, IDs, start and end coordinates, but also provide interactive operation for users to display, label and align the CRISPR sequences, which help researchers investigate the locations, orders and components of the CRISPR sequences in a global view. In comparison to other CRISPR visualization tools such as CRISPRviz and CRISPRStudio, CrisprVi not only improves the interactivity and effects of the visualization, but also provides basic statistics of the CRISPR sequences, and the consensus sequences of DRs/spacers across the input strains can be inspected from a clustering heatmap based on the BLAST results of the CRISPR sequences hitting against the genomes.

Conclusions: CrisprVi is a convenient tool for visualizing and analyzing the CRISPR sequences and it would be helpful for users to inspect novel CRISPR-Cas systems of prokaryotes.
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http://dx.doi.org/10.1186/s12859-022-04716-9DOI Listing
May 2022

Antibiotic cocktail-induced gut microbiota depletion in different stages could cause host cognitive impairment and emotional disorders in adulthood in different manners.

Neurobiol Dis 2022 Aug 16;170:105757. Epub 2022 May 16.

Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, PR China. Electronic address:

Gut microbiota depletion may result in cognitive impairment and emotional disorder. This study aimed to determine the possible association between host gut microbiota, cognitive function, and emotion in various life stages and its related underlying mechanisms. Seventy-five neonatal mice were randomly divided into five groups (n = 15 per group). Mice in the vehicle group were administered distilled water from birth to death, and those in the last four groups were administered antibiotic cocktail from birth to death, from birth to postnatal day (PND) 21 (infancy), from PND 21 to 56 (adolescence), and from PND 57 to 84 (adulthood), respectively. Antibiotic exposure consistently altered the gut microbiota composition and decreased the diversity of gut microbiota. Proteobacteria were the predominant bacteria instead of Firmicutes and Bacteroidetes after antibiotic exposure in different life stages. Long-term and infant gut microbiota depletion resulted in anxiety- and depression-like behaviors, memory impairments, and increased expression of γ-aminobutyric acid type A receptor α1 of adult mice. Long-term antibiotic exposure also significantly decreased serum interleukin (IL)-1β, IL-10, and corticosterone of adult mice. Gut microbiota depletion in adolescence resulted in anxiety-like behaviors, short-term memory decline, decreased serum interferon-γ (IFN-γ), mRNA expression of 5-hydroxytryptamine receptor 1A, and neuropeptide Y receptor Y2 in the prefrontal cortex of adult mice. Antibiotic exposure in adulthood damaged short-term memory and decreased serum IL-10, IFN-γ, and increased γ-aminobutyric acid type B receptor 1 mRNA expression of adult mice. These results suggest that antibiotic-induced gut microbiota depletion in the long term and infancy resulted in the most severe cognitive and emotional disorders followed by depletion in adolescence and adulthood. These results also suggest that gut microbes could influence host cognitive function and emotion in a life stage-dependent manner by affecting the function of the immune system, hypothalamic-pituitary-adrenal axis, and the expression of neurochemicals in the brain.
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http://dx.doi.org/10.1016/j.nbd.2022.105757DOI Listing
August 2022

N-methyladenosine modifications of mRNAs and long noncoding RNAs in oxygen-induced retinopathy in mice.

Exp Eye Res 2022 Jul 15;220:109114. Epub 2022 May 15.

Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. Electronic address:

Retinal neovascular diseases are major causes of blindness worldwide. As a common epitranscriptomic modification of eukaryotic RNAs, N-methyladenosine (mA) is associated with the pathogenesis of many diseases, including angiogenesis, through the regulation of RNA metabolism and functions. The aim of this study was to identify mA modifications of mRNAs and long noncoding RNAs (lncRNAs) and determine their potential roles in retinal neovascularization. The transcriptome-wide mA profiles of mRNAs and lncRNAs in the retinal tissues of mice with oxygen-induced retinopathy (OIR) and controls were identified by microarray analysis of immunoprecipitated methylated RNAs. The mA methylation levels of mRNAs and lncRNAs identified in the microarray data were validated by MeRIP-qPCR. A total of 1321 mRNAs (151 hypermethylated and 1170 hypomethylated) and 192 lncRNAs (15 hypermethylated and 177 hypomethylated) were differentially methylated with the mA modification in OIR and control mice. Gene ontology analysis showed that hypermethylated mRNAs were enriched in the regulation of multicellular organismal process, intracellular organelle, and protein binding, while hypomethylated mRNAs were enriched in cellular metabolic process, intracellular process, and binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that hypermethylated mRNAs were involved in dopaminergic synapses, glutamatergic synapse, and PI3K-Akt signaling pathway, while hypomethylated mRNAs were involved in autophagy, ubiquitin-mediated proteolysis, and spliceosome. Moreover, the altered levels of mA methylation of ANGPT2, GNG12, ROBO4, and ENSMUST00000153785 were validated by MeRIP-qPCR. The results revealed an altered mA epitranscriptome in OIR retinas. These methylated RNAs may act as novel modulators and targets in retinal neovascularization.
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http://dx.doi.org/10.1016/j.exer.2022.109114DOI Listing
July 2022

Systematic screening and structural characterization of dipeptides using offline 2D LC-LTQ-Orbitrap MS: A case study of .

J Pharm Anal 2022 Apr 21;12(2):263-269. Epub 2021 Jul 21.

Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for Traditional Chinese Medicine Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

() is a widely used and highly valuable traditional Chinese medicine. Several dipeptides have been detected in , but current scientific knowledge of its chemical makeup remains limited. In this study, an improved approach that integrates offline two-dimensional liquid chromatography (2D LC) separation, precursor ion list, library screening, and diagnostic ion filtering was established to systematically screen and characterize dipeptides in . Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides. A library containing the potential 400 dipeptides was created, and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity. To identify dipeptides, the type and connection sequence of amino acids were determined according to the product ions. Ile and Leu residues were differentiated for the first time according to the characteristic ion at 69.07. Ultimately, 170 dipeptides were identified or tentatively characterized from , and most are reported for the first time in this species herein. In addition, the identified dipeptides were also applied for discrimination among the three species, and 11 markers were identified. The obtained results provide a deeper understanding of the chemical basis of
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http://dx.doi.org/10.1016/j.jpha.2021.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091903PMC
April 2022

Research on Carbon Emissions Reduction Strategy Considering Government Subsidy and Free Riding Behavior.

Environ Eng Sci 2022 Apr 13;39(4):329-341. Epub 2022 Apr 13.

School of Economics and Management, Anhui University of Science and Technology, Huainan, China.

Government subsidy can greatly encourage supply chain enterprises to reduce carbon emissions. To quickly occupy the market, supply chain enterprises form alliances. However, enterprises in the alliance have speculative psychology, and the impact of such free riding behavior on the carbon emissions reduction willingness of supply chain enterprises is still unclear. In this article, government subsidies and free riding behavior parameters are introduced to build a carbon emissions reduction decision model for the government, manufacturers, and suppliers, and the impact of government subsidies and free riding behavior on the decision making of supply chain enterprises is analyzed through evolutionary game theory. The analysis shows that government subsidies have an incentive effect on carbon emissions reduction of supply chain enterprises. After the market stabilizes, even if the government subsidies are gradually withdrawn, the carbon emissions reduction of supply chain enterprises still converges to Pareto optimal equilibrium. The influence of free riding behavior on supply chain enterprises depends on the carbon emissions reduction profit. When the carbon emissions reduction profit is different, the decision of manufacturers and suppliers will be different. The above conclusions provide a reference for governments to strengthen control or enterprises to make decisions on carbon emissions reduction.
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http://dx.doi.org/10.1089/ees.2021.0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051875PMC
April 2022
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